Circular RNAs in cancer

Abstract

Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as a significant focus in RNA research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles in diverse physiological and pathological processes, functioning through mechanisms such as miRNAs or proteins sponging, regulation of splicing and gene expression, and serving as translation templates, particularly in the context of various cancers. The hallmarks of cancer comprise functional capabilities acquired during carcinogenesis and tumor progression, providing a conceptual framework that elucidates the nature of the malignant transformation. Although numerous studies have elucidated the role of circRNAs in the hallmarks of cancers, their functions in the development of chemoradiotherapy resistance remain unexplored and the clinical applications of circRNA-based translational therapeutics are still in their infancy. This review provides a comprehensive overview of circRNAs, covering their biogenesis, unique characteristics, functions, and turnover mechanisms. We also summarize the involvement of circRNAs in cancer hallmarks and their clinical relevance as biomarkers and therapeutic targets, especially in thyroid cancer (TC). Considering the potential of circRNAs as biomarkers and the fascination of circRNA-based therapeutics, the “Ying-Yang” dynamic regulations of circRNAs in TC warrant vastly dedicated investigations.

Keywords

biomarker / circular RNA / hallmarks of cancer / therapeutic targets / thyroid cancer

References

[1] Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012; 9(6): 703-719.

[2] Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483): 344-352.

[3] Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells. Nature. 2012; 489(7414): 101-108.

[4] Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Nat Acad Sci USA. 1976; 73(11): 3852-3856.

[5] Kristensen LS, Jakobsen T, Hager H, Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022; 19(3): 188-206.

[6] Guo Y, Yang J, Huang Q, et al. Circular RNAs and their roles in head and neck cancers. Mol Cancer. 2019; 18(1): 44.

[7] Liu M, Zhao J. Circular RNAs in diabetic nephropathy: updates and perspectives. Aging Dis. 2022; 13(5): 1365-1380.

[8] Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013; 495(7441): 384-388.

[9] Cerda-Jara CA, Kim SJ, Thomas G, et al. miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner. EMBO Rep. 2024; 25(7): 3008-3039.

[10] Gu X, Li X, Jin Y, et al. CDR1as regulated by hnRNPM maintains stemness of periodontal ligament stem cells via miR-7/KLF4. J Cell Mol Med. 2021; 25(9): 4501-4515.

[11] Mehta SL, Chokkalla AK, Bathula S, Arruri V, Chelluboina B, Vemuganti R. CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability. Mol Ther Nucleic Acids. 2023; 31: 57-67.

[12] Scoyni F, Sitnikova V, Giudice L, et al. ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling. Cell Rep. 2024; 43(3): 113862.

[13] Shao Y, Xu J, Liang B, et al. The role of CDR1as/ciRS-7 in cardio-cerebrovascular diseases. Biomed Pharmacother. 2023; 167: 115589.

[14] Yang H, Chen J, Liu S, et al. Exosomes from IgE-stimulated mast cells aggravate asthma-mediated atherosclerosis through circRNA CDR1as-mediated endothelial cell dysfunction in mice. Arterioscler Thromb Vasc Biol. 2024; 44(3): e99-e115.

[15] Zhong G, Zhao Q, Chen Z, Yao T. TGF-β signaling promotes cervical cancer metastasis via CDR1as. Mol Cancer. 2023; 22(1): 66.

[16] Mao W, Wang K, Xu B, et al. ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma. Mol Cancer. 2021; 20(1): 142.

[17] Mecozzi N, Vera O, Karreth FA. Squaring the circle: circRNAs in melanoma. Oncogene. 2021; 40(37): 5559-5566.

[18] Chen J, Yang J, Fei X, Wang X, Wang K. CircRNA ciRS-7: a novel oncogene in multiple cancers. Int J Biol Sci. 2021; 17(1): 379-389.

[19] Kitahara CM, Sosa JA. The changing incidence of thyroid cancer. Nat Rev Endocrinol. 2016; 12(11): 646-653.

[20] Lee JC, Gundara JS, Glover A, Serpell J, Sidhu SB. MicroRNA expression profiles in the management of papillary thyroid cancer. Oncologist. 2014; 19(11): 1141-1147.

[21] Hamidi AA, Taghehchian N, Basirat Z, Zangouei AS, Moghbeli M. MicroRNAs as the critical regulators of cell migration and invasion in thyroid cancer. Biomark Res. 2022; 10(1): 40.

[22] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-674.

[23] Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022; 12(1): 31-46.

[24] Su M, Xiao Y, Ma J, et al. Circular RNAs in cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers. Mol Cancer. 2019; 18(1): 90.

[25] Kristensen LS, Hansen TB, Veno MT, Kjems J. Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2018; 37(5): 555-565.

[26] Li Z, Cheng Y, Wu F, et al. The emerging landscape of circular RNAs in immunity: breakthroughs and challenges. Biomark Res. 2020; 8(1): 25.

[27] Chen Z-Q, Zuo X-L, Cai J, et al. Hypoxia-associated circPRDM4 promotes immune escape via HIF-1α regulation of PD-L1 in hepatocellular carcinoma. Exp Hematol Oncol. 2023; 12(1): 17.

[28] Swanton C, Bernard E, Abbosh C, et al. Embracing cancer complexity: hallmarks of systemic disease. Cell. 2024; 187(7): 1589-1616.

[29] Dakal TC, Dhabhai B, Pant A, et al. Oncogenes and tumor suppressor genes: functions and roles in cancers. MedComm. 2024; 5(6): e582.

[30] Zhao Z, Deng Y, Han J, et al. CircMALAT1 promotes cancer stem-like properties and chemoresistance via regulating Musashi-2/c-Myc axis in esophageal squamous cell carcinoma. MedComm. 2024; 5(6): e612.

[31] Papatsirou M, Artemaki PI, Karousi P, Scorilas A, Kontos CK. Circular RNAs: emerging regulators of the major signaling pathways involved in cancer progression. Cancers. 2021; 13(11): 2744.

[32] Lebastchi AH, Callender GG. Thyroid cancer. Curr Probl Cancer. 2014; 38(2): 48-74.

[33] Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013; 2013: 1-10.

[34] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66(1): 7-30.

[35] Zhou T, Wang X, Zhang J, et al. Global burden of thyroid cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. J Hematol Oncol. 2024; 17(1): 74.

[36] Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA. 2024; 331(5): 425-435.

[37] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2): 115-132.

[38] Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China. J Natl Cancer Center. 2016; 2(1): 1-9.

[39] Li J, Zhang Y, Dong P-Y, Yang G-M, Gurunathan S. A comprehensive review on the composition, biogenesis, purification, and multifunctional role of exosome as delivery vehicles for cancer therapy. Biomed Pharmacother. 2023; 165: 115087.

[40] Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017; 317(13): 1338.

[41] Viola D, Elisei R. Management of medullary thyroid cancer. Endocrinol Metab Clin North Am. 2019; 48(1): 285-301.

[42] Ernani V, Kumar M, Chen AY, Owonikoko TK. Systemic treatment and management approaches for medullary thyroid cancer. Cancer Treat Rev. 2016; 50: 89-98.

[43] Kushchayev SV, Kushchayeva YS, Tella SH, Glushko T, Pacak K, Teytelboym OM. Medullary thyroid carcinoma: an update on imaging. Journal of Thyroid Research. 2019; 2019: 1893047.

[44] Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. The Lancet. 2016; 388(10061): 2783-2795.

[45] Santhanam P, Ladenson PW. Surveillance for differentiated thyroid cancer recurrence. Endocrinol Metab Clin North Am. 2019; 48(1): 239-252.

[46] Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K, Miyauchi A. Prognostic factors for recurrence of papillary thyroid carcinoma in the lymph nodes, lung, and bone: analysis of 5, 768 patients with average 10-year follow-up. World J Surg. 2012; 36(6): 1274-1278.

[47] Schlumberger M, Leboulleux S. Current practice in patients with differentiated thyroid cancer. Nat Rev Endocrinol. 2021; 17(3): 176-188.

[48] Grønlund MP, Jensen JS, Hahn CH, Grønhøj C, Buchwald CV. Risk factors for recurrence of follicular thyroid cancer: a systematic review. Thyroid. 2021; 31(10): 1523-1530.

[49] Xu T, Wu J, Han P, Zhao Z, Song X. Circular RNA expression profiles and features in human tissues: a study using RNA-seq data. BMC Genomics. 2017; 18(Suppl 6): 680.

[50] Lima CR, Gomes CC, Santos MF. Role of microRNAs in endocrine cancer metastasis. Mol Cell Endocrinol. 2017; 456: 62-75.

[51] Kentwell J, Gundara JS, Sidhu SB. Noncoding RNAs in endocrine malignancy. Oncologist. 2014; 19(5): 483-491.

[52] Papatsirou M, Artemaki PI, Scorilas A, Kontos CK. The role of circular RNAs in therapy resistance of patients with solid tumors. Per Med. 2020; 17(6): 469-490.

[53] Liu W, Zhao J, Jin M, Zhou M. circRAPGEF5 contributes to papillary thyroid proliferation and metastatis by regulation miR-198/FGFR1. Mol Ther Nucleic Acids. 2019; 14: 609-616.

[54] Luo Q, Guo F, Fu Q, Sui G. hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G(1)/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4. Mol Ther Nucleic Acids. 2021; 24: 591-609.

[55] Peng N, Shi L, Zhang Q, Hu Y, Wang N, Ye H. Microarray profiling of circular RNAs in human papillary thyroid carcinoma. PLoS One. 2017; 12(3): e0170287.

[56] Ren H, Liu Z, Liu S, et al. Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma. PeerJ. 2018; 6: e5363.

[57] Wei H, Pan L, Tao D, Li R. Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression. Biochem Biophys Res Commun. 2018; 503(1): 56-61.

[58] Lasda E, Parker R. Circular RNAs: diversity of form and function. RNA. 2014; 20(12): 1829-1842.

[59] Li Y, Zheng F, Xiao X, et al. CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 2017; 18(9): 1646-1659.

[60] Huang W, Fang K, Chen TQ, et al. circRNA circAF4 functions as an oncogene to regulate MLL-AF4 fusion protein expression and inhibit MLL leukemia progression. J Hematol Oncol. 2019; 12(1): 103.

[61] Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3): 256-264.

[62] Zhang Y, Zhang X-O, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell. 2013; 51(6): 792-806.

[63] Visci G, Tolomeo D, Agostini A, Traversa D, Macchia G, Storlazzi CT. CircRNAs and fusion-circRNAs in cancer: new players in an old game. Cell Signal. 2020; 75: 109747.

[64] Vo JN, Cieslik M, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019; 176(4): 869-881.e13.

[65] Guarnerio J, Bezzi M, Jeong JC, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 2016; 165(2): 289-302.

[66] Tan S, Gou Q, Pu W, et al. Circular RNA F-circEA produced from EML4-ALK fusion gene as a novel liquid biopsy biomarker for non-small cell lung cancer. Cell Res. 2018; 28(6): 693-695.

[67] Tan S, Sun D, Pu W, et al. Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer. Mol Cancer. 2018; 17(1): 138.

[68] Vidal AF. Read-through circular RNAs reveal the plasticity of RNA processing mechanisms in human cells. RNA Biol. 2020; 17(12): 1823-1826.

[69] Wawrzyniak O, Zarebska Z, Kuczynski K, Gotz-Wieckowska A, Rolle K. Protein-related circular RNAs in human pathologies. Cells. 2020; 9(8): 1841.

[70] Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019; 20(11): 675-691.

[71] Barrett SP, Wang PL, Salzman J. Circular RNA biogenesis can proceed through an exon-containing lariat precursor. eLife. 2015; 4: e07540.

[72] Kelly S, Greenman C, Cook PR, Papantonis A. Exon skipping is correlated with exon circularization. J Mol Biol. 2015; 427(15): 2414-2417.

[73] Geng Y, Jiang J, Wu C. Function and clinical significance of circRNAs in solid tumors. J Hematol Oncol. 2018; 11(1): 98.

[74] Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013; 19(2): 141-157.

[75] Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016; 7: 11215.

[76] Enuka Y, Lauriola M, Feldman ME, Sas-Chen A, Ulitsky I, Yarden Y. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res. 2016; 44(3): 1370-1383.

[77] Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 2012; 7(2): e30733.

[78] Rybak-Wolf A, Stottmeister C, Glazar P, et al. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell. 2015; 58(5): 870-885.

[79] Venø MT, Hansen TB, Venø ST, et al. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol. 2015; 16(1): 245.

[80] Errichelli L, Dini Modigliani S, Laneve P, et al. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nat Commun. 2017; 8: 14741.

[81] Nicolet BP, Engels S, Aglialoro F, van den Akker E, von Lindern M, Wolkers MC. Circular RNA expression in human hematopoietic cells is widespread and cell-type specific. Nucleic Acids Res. 2018; 46(16): 8168-8180.

[82] Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet. 2013; 9(9): e1003777.

[83] Yao W, Li Y, Han L, et al. The CDR1as/miR-7/TGFBR2 axis modulates EMT in silica-induced pulmonary fibrosis. Toxicol Sci. 2018; 166(2): 465-478.

[84] Li P, Yang X, Yuan W, et al. CircRNA-Cdr1as exerts anti-oncogenic functions in bladder cancer by sponging microRNA-135a. Cell Physiol Biochem: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2018; 46(4): 1606-1616.

[85] Xu L, Zhang M, Zheng X, Yi P, Lan C, Xu M. The circular RNA ciRS-7 (Cdr1as) acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2017; 143(1): 17-27.

[86] Fan G-C, Geng H-H, Li R, et al. The circular RNA Cdr1as promotes myocardial infarction by mediating the regulation of miR-7a on its target genes expression. PLoS One. 2016; 11(3): e0151753.

[87] Xu H, Guo S, Li W, Yu P. The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells. Sci Rep. 2015; 5: 12453.

[88] Xie Y, Yuan X, Zhou W, et al. The circular RNA HIPK3 (circHIPK3) and its regulation in cancer progression: review. Life Sci. 2020; 254: 117252.

[89] Wilusz JE. A 360 degrees view of circular RNAs: from biogenesis to functions. Wiley Interdiscip Rev RNA. 2018; 9(4): e1478.

[90] Yang Q, Li F, He AT, Yang BB. Circular RNAs: expression, localization, and therapeutic potentials. Mol Ther. 2021; 29(5): 1683-1702.

[91] Li X, Liu C-X, Xue W, et al. Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol Cell. 2017; 67(2): 214-227.e7.

[92] Zeng Y, Du WW, Wu Y, et al. A circular RNA binds to and activates AKT phosphorylation and nuclear localization reducing apoptosis and enhancing cardiac repair. Theranostics. 2017; 7(16): 3842-3855.

[93] Wu N, Xu J, Du WW, et al. YAP circular RNA, circYap, attenuates cardiac fibrosis via binding with tropomyosin-4 and gamma-actin decreasing actin polymerization. Mol Ther. 2021; 29(3): 1138-1150.

[94] Du WW, Yang W, Li X, et al. The circular RNA circSKA3 binds integrin β1 to induce invadopodium formation enhancing breast cancer invasion. Mol Ther. 2020; 28(5): 1287-1298.

[95] Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L. Complementary sequence-mediated exon circularization. Cell. 2014; 159(1): 134-147.

[96] Wang L, Long H, Zheng Q, Bo X, Xiao X, Li B. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer. 2019; 18(1): 119.

[97] Barbagallo D, Caponnetto A, Brex D, et al. CircSMARCA5 regulates VEGFA mRNA splicing and angiogenesis in glioblastoma multiforme through the binding of SRSF1. Cancers. 2019; 11(2): 194.

[98] Li S, Li X, Xue W, et al. Screening for functional circular RNAs using the CRISPR-Cas13 system. Nat Methods. 2021; 18(1): 51-59.

[99] Wu N, Yuan Z, Du KY, et al. Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery. Cell Death Differ. 2019; 26(12): 2758-2773.

[100] Ma J, Du WW, Zeng K, et al. An antisense circular RNA circSCRIB enhances cancer progression by suppressing parental gene splicing and translation. Mol Ther. 2021; 29(9): 2754-2768.

[101] Lei M, Zheng G, Ning Q, Zheng J, Dong D. Translation and functional roles of circular RNAs in human cancer. Mol Cancer. 2020; 19(1): 30.

[102] Song R, Ma S, Xu J, et al. A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR. Mol Cancer. 2023; 22(1): 16.

[103] Zhang L, Gao H, Li X, Yu F, Li P. The important regulatory roles of circRNA-encoded proteins or peptides in cancer pathogenesis (Review). Int J Oncol. 2024; 64(2): 19.

[104] Sinha T, Panigrahi C, Das D, Chandra Panda A. Circular RNA translation, a path to hidden proteome. Wiley Interdiscip Rev RNA. 2022; 13(1): e1685.

[105] Zheng X, Chen L, Zhou Y, et al. A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer. 2019; 18(1): 47.

[106] Li Y, Chen B, Zhao J, et al. HNRNPL circularizes ARHGAP35 to produce an oncogenic protein. Adv Sci (Weinh). 2021; 8(13): 2001701.

[107] Zhao J, Lee EE, Kim J, et al. Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus. Nat Commun. 2019; 10(1): 2300.

[108] Wang X, Jian W, Luo Q, Fang L. CircSEMA4B inhibits the progression of breast cancer by encoding a novel protein SEMA4B-211aa and regulating AKT phosphorylation. Cell Death Dis. 2022; 13(9): 794.

[109] Ye F, Gao G, Zou Y, et al. circFBXW7 inhibits malignant progression by sponging miR-197-3p and encoding a 185-aa protein in triple-negative breast cancer. Mol Ther Nucleic Acids. 2019; 18: 88-98.

[110] Wang S, Latallo MJ, Zhang Z, et al. Nuclear export and translation of circular repeat-containing intronic RNA in C9ORF72-ALS/FTD. Nat Commun. 2021; 12(1): 4908.

[111] Huang C, Liang D, Tatomer DC, Wilusz JE. A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev. 2018; 32(9-10): 639-644.

[112] Chen RX, Chen X, Xia LP, et al. N(6)-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun. 2019; 10(1): 4695.

[113] Talhouarne GJS, Gall JG. Lariat intronic RNAs in the cytoplasm of vertebrate cells. Proc Natl Acad Sci USA. 2018; 115(34): E7970-E7977.

[114] Zhou M, Xiao MS, Li Z, Huang C. New progresses of circular RNA biology: from nuclear export to degradation. RNA Biol. 2021; 18(10): 1365-1373.

[115] Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J. 2011; 30(21): 4414-4422.

[116] Park OH, Ha H, Lee Y, et al. Endoribonucleolytic cleavage of m(6)A-containing RNAs by RNase P/MRP complex. Mol Cell. 2019; 74(3): 494-507.

[117] Liu CX, Li X, Nan F, et al. Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell. 2019; 177(4): 865-880.e21.

[118] Fischer JW, Busa VF, Shao Y, Leung AKL. Structure-mediated RNA decay by UPF1 and G3BP1. Mol Cell. 2020; 78(1): 70-84.e6.

[119] Guo Y, Wei X, Peng Y. Structure-mediated degradation of CircRNAs. Trends Cell Biol. 2020; 30(7): 501-503.

[120] Jia R, Xiao MS, Li Z, Shan G, Huang C. Defining an evolutionarily conserved role of GW182 in circular RNA degradation. Cell Discov. 2019; 5: 45.

[121] Liu J, Ren L, Li S, et al. The biology, function, and applications of exosomes in cancer. Acta Pharm Sin B. 2021; 11(9): 2783-2797.

[122] Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015; 25(8): 981-984.

[123] Lasda E, Parker R. Circular RNAs co-precipitate with extracellular vesicles: a possible mechanism for circRNA clearance. PLoS One. 2016; 11(2): e0148407.

[124] Sun H, Wu Z, Liu M, et al. CircRNA may not be “circular”. Front Genet. 2021; 12: 633750.

[125] Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1): 57-70.

[126] Huang G, Liang M, Liu H, et al. CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway. Cell Death Dis. 2020; 11(12): 1065.

[127] Wu B, Xia L, Zhang S, et al. circRNA-SMO upregulates CEP85 to promote proliferation and migration of glioblastoma via sponging miR-326. Histol Histopathol. 2023; 38(11): 1307-1319.

[128] Yang F, Ma Q, Huang B, et al. CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability. J Transl Med. 2023; 21(1): 402.

[129] Yan X, Zhang M, Li B, Ji X, Wu H, Zhang Q. RAI14 regulated by circNFATC3/miR-23b-3p axis facilitates cell growth and invasion in gastric cancer. Cell Transplant. 2021; 30: 9636897211007055.

[130] Long MY, Chen JW, Zhu Y, et al. Comprehensive circular RNA profiling reveals the regulatory role of circRNA_0007694 in papillary thyroid carcinoma. Am J Transl Res. 2020; 12(4): 1362-1378.

[131] Wang M, Chen B, Ru Z, Cong L. CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/beta-catenin pathway. Biochem Biophys Res Commun. 2018; 504(1): 283-288.

[132] Bi W, Huang J, Nie C, et al. CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of β-catenin pathway. J Exp Clin Cancer Res. 2018; 37(1): 275-275.

[133] Yao Y, Chen X, Yang H, et al. Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasiveness through the NOTCH3/GATAD2A axis. J Exp Clin Cancer Res. 2019; 38(1): 318-318.

[134] Liu L, Yan C, Tao S, Wang H. Circ_0058124 aggravates the progression of papillary thyroid carcinoma by activating LMO4 expression via targeting miR-370-3p. Cancer Manag Res. 2020; 12: 9459-9470.

[135] Jin X, Wang Z, Pang W, et al. Upregulated hsa_circ_0004458 contributes to progression of papillary thyroid carcinoma by inhibition of miR-885-5p and activation of RAC1. Med Sci Monit. 2018; 24: 5488-5500.

[136] Zhu J, Wang Y, Yang C, et al. circ-PSD3 promoted proliferation and invasion of papillary thyroid cancer cells via regulating the miR-7-5p/METTL7B axis. J Recept Signal Transduct Res. 2021: 1-10.

[137] Li Z, Huang X, Liu A, et al. Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis. Life Sci. 2021; 264: 118622.

[138] Wang H, Yan X, Zhang H, Zhan X. CircRNA circ_0067934 overexpression correlates with poor prognosis and promotes thyroid carcinoma progression. Med Sci Monit: International Medical Journal of Experimental and Clinical Research. 2019; 25: 1342-1349.

[139] Zhang H, Ma XP, Li X, Deng FS. Circular RNA circ_0067934 exhaustion expedites cell apoptosis and represses cell proliferation, migration and invasion in thyroid cancer via sponging miR-1304 and regulating CXCR1 expression. Eur Rev Med Pharmacol Sci. 2019; 23(24): 10851-10866.

[140] Fagerberg L, Hallström BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014; 13(2): 397-406.

[141] Zhang Z, Xia F, Yao L, Jiang B, Li X. circSSU72 promotes cell proliferation, migration and invasion of papillary thyroid carcinoma cells by targeting miR-451a/S1PR2 axis. Front Cell Dev Biol. 2022; 10: 817028.

[142] Li C, Zhu L, Fu L, et al. CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways. Diagn Pathol. 2021; 16(1): 93.

[143] Zhang W, Zhang H, Zhao X. circ_0005273 promotes thyroid carcinoma progression by SOX2 expression. Endocr Relat Cancer. 2020; 27(1): 11-21.

[144] Han JY, Guo S, Wei N, et al. ciRS-7 promotes the proliferation and migration of papillary thyroid cancer by negatively regulating the miR-7/epidermal growth factor receptor axis. Biomed Res Int. 2020; 2020: 9875636.

[145] Gong J, Kong X, Qi J, Lu J, Yuan S, Wu M. CircRNA_104565 promoted cell proliferation in papillary thyroid carcinoma by sponging miR-134. Int J Gen Med. 2021; 14: 179-185.

[146] Liu J, Li H, Wei C, et al. circFAT1(e2) promotes papillary thyroid cancer proliferation, migration, and invasion via the miRNA-873/ZEB1 axis. Comput Math Methods Med. 2020; 2020: 1459368.

[147] Ma W, Zhao P, Zang L, Zhang K, Liao H, Hu Z. CircTP53 promotes the proliferation of thyroid cancer via targeting miR-1233-3p/MDM2 axis. J Endocrinol Invest. 2021; 44(2): 353-362.

[148] Wang W, Huang C, Luo P, et al. Circular RNA circWDR27 promotes papillary thyroid cancer progression by regulating miR-215-5p/TRIM44 axis. Onco Targets Ther. 2021; 14: 3281-3293.

[149] Tan X, Zhao J, Lou J, Zheng W, Wang P. Hsa_circ_0058129 regulates papillary thyroid cancer development via miR-873-5p/follistatin-like 1 axis. J Clin Lab Anal. 2022; 36(5): e24401.

[150] Wu G, Zhou W, Pan X, et al. Circular RNA profiling reveals exosomal circ_0006156 as a novel biomarker in papillary thyroid cancer. Mol Ther Nucleic Acids. 2020; 19: 1134-1144.

[151] Ye M, Hou H, Shen M, Dong S, Zhang T. Circular RNA circFOXM1 plays a role in papillary thyroid carcinoma by sponging miR-1179 and regulating HMGB1 expression. Mol Ther Nucleic Acids. 2020; 19: 741-750.

[152] Pan Y, Xu T, Liu Y, Li W, Zhang W. Upregulated circular RNA circ_0025033 promotes papillary thyroid cancer cell proliferation and invasion via sponging miR-1231 and miR-1304. Biochem Biophys Res Commun. 2019; 510(2): 334-338.

[153] Luan S, Fu P, Wang X, Gao Y, Shi K, Guo Y. Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression. J Int Med Res. 2020; 48(9): 300060520934659.

[154] Xue C, Cheng Y, Wu J, et al. Circular RNA CircPRMT5 accelerates proliferation and invasion of papillary thyroid cancer through regulation of miR-30c/E2F3 axis. Cancer Manag Res. 2020; 12: 3285-3291.

[155] Nie C, Han J, Bi W, et al. Circular RNA circ_0000644 promotes papillary thyroid cancer progression via sponging miR-1205 and regulating E2F3 expression. Cell Cycle. 2022; 21(2): 126-139.

[156] Qi Y, He J, Zhang Y, et al. Circular RNA hsa_circ_0001666 sponges miR-330-5p, miR-193a-5p and miR-326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4. Oncol Rep. 2021; 45(4).

[157] Mao Y, Huo Y, Li J, et al. circRPS28 (hsa_circ_0049055) is a novel contributor for papillary thyroid carcinoma by regulating cell growth and motility via functioning as ceRNA for miR-345-5p to regulate frizzled family receptor 8 (FZD8). Endocr J. 2021; 68(11): 1267-1281.

[158] Zhang D, Tao L, Xu N, et al. CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway. Cell Death Discov. 2022; 8(1): 21.

[159] Xia F, Chen Y, Jiang B, Bai N, Li X. Hsa_circ_0011385 accelerates the progression of thyroid cancer by targeting miR-361-3p. Cancer Cell Int. 2020; 20: 49.

[160] Cai X, Zhao Z, Dong J, et al. Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression. Cell Death Dis. 2019; 10(3): 184.

[161] Tao L, Yang L, Tian P, Guo X, Chen Y. Knockdown of circPVT1 inhibits progression of papillary thyroid carcinoma by sponging miR-126. RSC Adv. 2019; 9(23): 13316-13324.

[162] Liu J, Zheng X, Liu H. Hsa_circ_0102272 serves as a prognostic biomarker and regulates proliferation, migration and apoptosis in thyroid cancer. J Gene Med. 2020; 22(9): e3209.

[163] Ding W, Shi Y, Zhang H. Circular RNA circNEURL4 inhibits cell proliferation and invasion of papillary thyroid carcinoma by sponging miR-1278 and regulating LATS1 expression. Am J Transl Res. 2021; 13(6): 5911-5927.

[164] Liu F, Zhang J, Qin L, et al. Circular RNA EIF6 (Hsa_circ_0060060) sponges miR-144-3p to promote the cisplatin-resistance of human thyroid carcinoma cells by autophagy regulation. Aging. 2018; 10(12): 3806-3820.

[165] Wang HH, Ma JN, Zhan XR. Circular RNA Circ_0067934 attenuates ferroptosis of thyroid cancer cells by miR-545-3p/SLC7A11 signaling. Front Endocrinol. 2021; 12: 670031.

[166] Zheng H, Fu Q, Ma K, Shi S, Fu Y. Circ_0079558 promotes papillary thyroid cancer progression by binding to miR-26b-5p to activate MET/AKT signaling. Endocr J. 2021; 68(11): 1247-1266.

[167] Zeng L, Yuan S, Zhou P, Gong J, Kong X, Wu M. Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression. Bioengineered. 2021; 12(2): 11795-11810.

[168] Zhang Z, Wang W, Su Z, Zhang J, Cao H. Circ_0011058 facilitates proliferation, angiogenesis and radioresistance in papillary thyroid cancer cells by positively regulating YAP1 via acting as miR-335-5p sponge. Cell Signal. 2021; 88: 110155.

[169] Li Z, Xu J, Guan H, Lai J, Yang X, Ma J. Circ_0059354 aggravates the progression of papillary thyroid carcinoma by elevating ARFGEF1 through sponging miR-766-3p. J Endocrinol Invest. 2022; 45(4): 825-836.

[170] Wu G, Zhou W, Lin X, et al. circRASSF2 acts as ceRNA and promotes papillary thyroid carcinoma progression through miR-1178/TLR4 signaling pathway. Mol Ther Nucleic Acids. 2020; 19: 1153-1163.

[171] Zhang W, Liu T, Li T, Zhao X. Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis. Cancer Gene Ther. 2021; 28(3-4): 279-293.

[172] Gui X, Li Y, Zhang X, Su K, Cao W. Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis. Cancer Cell Int. 2020; 20: 241.

[173] Jiang YM, Liu W, Jiang L, Chang H. CircLDLR promotes papillary thyroid carcinoma tumorigenicity by regulating miR-637/LMO4 Axis. Dis Markers. 2021; 2021: 3977189.

[174] Ma J, Kan Z. Circular RNA circ_0008274 enhances the malignant progression of papillary thyroid carcinoma via modulating solute carrier family 7 member 11 by sponging miR-154-3p. Endocr J. 2021; 68(5): 543-552.

[175] Chu J, Tao L, Yao T, et al. Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression. Cell Death Dis. 2021; 12(1): 112.

[176] Xiang Y, Wang W, Gu J, Shang J. Circular RNA VANGL1 facilitates migration and invasion of papillary thyroid cancer by modulating the miR-194/ZEB1/EMT axis. J Oncol. 2022; 2022: 4818651.

[177] Li P, Chen J, Zou J, Zhu W, Zang Y, Li H. Circular RNA coiled-coil domain containing 66 regulates malignant development of papillary thyroid carcinoma by upregulating La ribonucleoprotein 1 via the sponge effect on miR-129-5p. Bioengineered. 2022; 13(3): 7181-7196.

[178] Wang YF, Li MY, Tang YF, Jia M, Liu Z, Li HQ. Circular RNA circEIF3I promotes papillary thyroid carcinoma progression through competitively binding to miR-149 and upregulating KIF2A expression. Am J Cancer Res. 2020; 10(4): 1130-1139.

[179] Wang Y, Zong H, Zhou H. Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis. Bioengineered. 2021; 12(1): 1484-1494.

[180] Yang Y, Ding L, Li Y, Xuan C. Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways. J Cell Physiol. 2020; 235(2): 1321-1329.

[181] Hu Z, Zhao P, Zhang K, Zang L, Liao H, Ma W. Hsa_circ_0011290 regulates proliferation, apoptosis and glycolytic phenotype in papillary thyroid cancer via miR-1252/FSTL1 signal pathway. Arch Biochem Biophys. 2020; 685: 108353.

[182] Wang L, Wang W, Cai Y, et al. Circ-NUP214 promotes papillary thyroid carcinoma tumorigenesis by regulating HK2 expression through miR-15a-5p. Biochem Genet. 2022; 60(4): 1408.

[183] Li X, Tian Y, Hu Y, Yang Z, Zhang L, Luo J. CircNUP214 sponges miR-145 to promote the expression of ZEB2 in thyroid cancer cells. Biochem Biophys Res Commun. 2018; 507(1-4): 168-172.

[184] Liu Y, Chen G, Wang B, Wu H, Zhang Y, Ye H. Silencing circRNA protein kinase C iota (circ-PRKCI) suppresses cell progression and glycolysis of human papillary thyroid cancer through circ-PRKCI/miR-335/E2F3 ceRNA axis. Endocr J. 2021; 68(6): 713-727.

[185] Sun D, Chen L, Lv H, Gao Y, Liu X, Zhang X. Circ_0058124 upregulates MAPK1 expression to promote proliferation, metastasis and metabolic abilities in thyroid cancer through sponging miR-940. Onco Targets Ther. 2020; 13: 1569-1581.

[186] Chen W, Zhang T, Bai Y, et al. Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer. Gland Surg. 2021; 10(8): 2500-2510.

[187] Li Y, Qin J, He Z, Cui G, Zhang K, Wu B. Knockdown of circPUM1 impedes cell growth, metastasis and glycolysis of papillary thyroid cancer via enhancing MAPK1 expression by serving as the sponge of miR-21-5p. Genes Genomics. 2021; 43(2): 141-150.

[188] Zhang S, Wang Q, Li D, et al. Oncolytic vaccinia virus-mediated antitumor effect and cell proliferation were promoted in PTC by regulating circRNA_103598/miR-23a-3p/IL-6 axis. Cancer Manag Res. 2020; 12: 10389-10396.

[189] Sa R, Guo M, Liu D, Guan F. AhR antagonist promotes differentiation of papillary thyroid cancer via regulating circSH2B3/miR-4640-5P/IGF2BP2 axis. Front Pharmacol. 2021; 12: 795386.

[190] Lou J, Hao Y, Lin K, et al. Circular RNA CDR1as disrupts the p53/MDM2 complex to inhibit gliomagenesis. Mol Cancer. 2020; 19(1): 138.

[191] Yang R, Chen H, Xing L, et al. Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10. Mol Cancer. 2022; 21(1): 88.

[192] Zhou M, Yang Z, Wang D, Chen P, Zhang Y. The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex. J Exp Clin Cancer Res. 2021; 40(1): 48.

[193] Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003; 1(14): 1001-1008.

[194] Zheng T, Chen W, Wang X, Cai W, Wu F, Lin C. Circular RNA circ-FAM158A promotes retinoblastoma progression by regulating miR-138-5p/SLC7A5 axis. Exp Eye Res. 2021; 211: 108650.

[195] Yuan Y, Zhou X, Kang Y, et al. Circ-CCS is identified as a cancer-promoting circRNA in lung cancer partly by regulating the miR-383/E2F7 axis. Life Sci. 2021; 267: 118955.

[196] Zou FW, Tang YF, Li X, Liu C, Wu C, Zhang LY. circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway. Sci Rep. 2024; 14(1): 22004.

[197] Ma S, Xu Y, Qin X, et al. RUNX1, FUS, and ELAVL1-induced circPTPN22 promote gastric cancer cell proliferation, migration, and invasion through miR-6788-5p/PAK1 axis-mediated autophagy. Cell Mol Biol Lett. 2024; 29(1): 95.

[198] Wei G, Chen X, Ruan T, et al. Human gastric cancer progression and stabilization of ATG2B through RNF5 binding facilitated by autophagy-associated CircDHX8. Cell Death Dis. 2024; 15(6): 410.

[199] Martinez LA, Goluszko E, Chen HZ, et al. E2F3 is a mediator of DNA damage-induced apoptosis. Mol Cell Biol. 2010; 30(2): 524-536.

[200] Xiong Y, Kotian S, Zeiger MA, Zhang L, Kebebew E. miR-126-3p inhibits thyroid cancer cell growth and metastasis, and is associated with aggressive thyroid cancer. PLoS One. 2015; 10(8): e0130496.

[201] Wen Q, Zhao J, Bai L, Wang T, Zhang H, Ma Q. miR-126 inhibits papillary thyroid carcinoma growth by targeting LRP6. Oncol Rep. 2015; 34(4): 2202-2210.

[202] Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021; 31(2): 107-125.

[203] Li Q, Li K, Guo Q, Yang T. CircRNA circSTIL inhibits ferroptosis in colorectal cancer via miR-431/SLC7A11 axis. Environ Toxicol. 2023; 38(5): 981-989.

[204] Jiang Y, Zhao J, Li R, et al. CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis. J Exp Clin Cancer Res. 2022; 41(1): 307.

[205] Dratwa M, Wysoczańska B, Łacina P, Kubik T, Bogunia-Kubik K. TERT-regulation and roles in cancer formation. Front Immunol. 2020; 11: 589929.

[206] Zhang H, Zhang X, Yu J. Integrated analysis of altered lncRNA, circRNA, microRNA, and mRNA expression in hepatocellular carcinoma carrying TERT promoter mutations. J Hepatocell Carcinoma. 2022; 9: 1201-1215.

[207] Zhang XL, Xu LL, Wang F. Hsa_circ_0020397 regulates colorectal cancer cell viability, apoptosis and invasion by promoting the expression of the miR-138 targets TERT and PD-L1. Cell Biol Int. 2017; 41(9): 1056-1064.

[208] Wang C, Huo YK, Li MY, et al. [Circ_0000263 improves radiosensitivity of Hela cells by inhibiting the activity of telomerase protein through miR-338-3p/TERT]. Zhonghua Zhong Liu Za Zhi. 2024; 46(7): 676-685.

[209] Zong ZH, Du YP, Guan X, Chen S, Zhao Y. CircWHSC1 promotes ovarian cancer progression by regulating MUC1 and hTERT through sponging miR-145 and miR-1182. J Exp Clin Cancer Res. 2019; 38(1): 437.

[210] Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011; 473(7347): 298-307.

[211] Li X, Wang C, Zhang H, et al. circFNDC3B accelerates vasculature formation and metastasis in oral squamous cell carcinoma. Cancer Res. 2023; 83(9): 1459-1475.

[212] Ding P, Wu H, Wu J, et al. N6-methyladenosine modified circPAK2 promotes lymph node metastasis via targeting IGF2BPs/VEGFA signaling in gastric cancer. Oncogene. 2024; 43(34): 2548-2563.

[213] Zhang C, Hu J, Liu Z, et al. Hsa_circ_0000520 suppresses vasculogenic mimicry formation and metastasis in bladder cancer through Lin28a/PTEN/PI3K signaling. Cell Mol Biol Lett. 2024; 29(1): 118.

[214] Chi Q, Wang Z, Xu H, Li H, Song D. Circ_0000758 facilitates bladder cancer cell growth, migration and angiogenesis via severing as miR-1236-3p sponge. Biochem Genet. 2024.

[215] Payervand N, Pakravan K, Razmara E, et al. Exosomal circ_0084043 derived from colorectal cancer-associated fibroblasts promotes in vitro endothelial cell angiogenesis by regulating the miR-140-3p/HIF-1α/VEGF signaling axis. Heliyon. 2024; 10(11): e31584.

[216] Ronca R, Giacomini A, Rusnati M, Presta M. The potential of fibroblast growth factor/fibroblast growth factor receptor signaling as a therapeutic target in tumor angiogenesis. Expert Opin Ther Targets. 2015; 19(10): 1361-1377.

[217] Zhu X, Qiu C, Wang Y, et al. FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis. Proc Natl Acad Sci USA. 2022; 119(26): e2202631119.

[218] Liu YY, Zhang YY, Ran LY, et al. A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc. J Transl Med. 2024; 22(1): 507.

[219] Zeng K, Peng J, Xing Y, et al. A positive feedback circuit driven by m(6)A-modified circular RNA facilitates colorectal cancer liver metastasis. Mol Cancer. 2023; 22(1): 202.

[220] Yang J, Qi M, Fei X, Wang X, Wang K. Hsa_circRNA_0088036 acts as a ceRNA to promote bladder cancer progression by sponging miR-140-3p. Cell Death Dis. 2022; 13(4): 322.

[221] Suh YJ, Kwon H, Kim SJ, et al. Factors affecting the locoregional recurrence of conventional papillary thyroid carcinoma after surgery: a retrospective analysis of 3381 patients. Ann Surg Oncol. 2015; 22(11): 3543-3549.

[222] Guo K, Wang Z. Risk factors influencing the recurrence of papillary thyroid carcinoma: a systematic review and meta-analysis. Int J Clin Exp Pathol. 2014; 7(9): 5393-5403.

[223] Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells?. Trends Biochem Sci. 2016; 41(3): 211-218.

[224] Zhong Z, Yu J, Virshup DM, Madan B. Wnts and the hallmarks of cancer. Cancer Metastasis Rev. 2020; 39(3): 625-645.

[225] Shangguan H, Feng H, Lv D, Wang J, Tian T, Wang X. Circular RNA circSLC25A16 contributes to the glycolysis of non-small-cell lung cancer through epigenetic modification. Cell Death Dis. 2020; 11(6): 437.

[226] Ma Y, He X, Di Y, et al. Circular RNA LIPH promotes pancreatic cancer glycolysis and progression through sponge miR-769-3p and interaction with GOLM1. Clin Transl Med. 2024; 14(8): e70003.

[227] Rong Z, Xu J, Yang J, et al. CircRREB1 mediates metabolic reprogramming and stemness maintenance to facilitate pancreatic ductal adenocarcinoma progression. Cancer Res. 2024; 84(24): 4246-4263.

[228] Ma Y, Du S, Wang S, et al. Circ_0004674 regulation of glycolysis and proliferation mechanism of osteosarcoma through miR-140-3p/TCF4 pathway. J Biochem Mol Toxicol. 2024; 38(9): e23846.

[229] Mellman I, Chen DS, Powles T, Turley SJ. The cancer-immunity cycle: indication, genotype, and immunotype. Immunity. 2023; 56(10): 2188-2205.

[230] Liu Z, Wang T, She Y, et al. N(6)-methyladenosine-modified circIGF2BP3 inhibits CD8(+) T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. Mol Cancer. 2021; 20(1): 105.

[231] Li B, Zhu L, Lu C, et al. circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun. 2021; 12(1): 295.

[232] Huang D, Zhu X, Ye S, et al. Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides. Nature. 2024; 625(7995): 593-602.

[233] Jia L, Wang Y, Wang CY. circFAT1 promotes cancer stemness and immune evasion by promoting STAT3 activation. Adv Sci (Weinh). 2021; 8(13): 2003376.

[234] Chen Z, He L, Zhao L, et al. circREEP3 drives colorectal cancer progression via activation of FKBP10 transcription and restriction of antitumor immunity. Adv Sci (Weinh). 2022; 9(13): e2105160.

[235] Conn VM, Chinnaiyan AM, Conn SJ. Circular RNA in cancer. Nat Rev Cancer. 2024; 24(9): 597-613.

[236] Martínez-Jiménez F, Muiños F, Sentís I, et al. A compendium of mutational cancer driver genes. Nat Rev Cancer. 2020; 20(10): 555-572.

[237] Li M, Chen W, Cui J, et al. circCIMT silencing promotes cadmium-induced malignant transformation of lung epithelial cells through the DNA base excision repair pathway. Adv Sci (Weinh). 2023; 10(14): e2206896.

[238] Xu X, Zhang J, Tian Y, et al. CircRNA inhibits DNA damage repair by interacting with host gene. Mol Cancer. 2020; 19(1): 128.

[239] Xu L, Ma X, Zhang X, et al. hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma. Mol Cancer. 2023; 22(1): 195.

[240] Song H, Liu Q, Liao Q. Circular RNA and tumor microenvironment. Cancer Cell Int. 2020; 20: 211.

[241] Sun Q, Yang Z, Qiu M, et al. Inflammatory factor TNFα-induced circDMD mediates R-loop formation to promote tumorigenesis. Int J Biol Macromol. 2024; 280(Pt 1):135689.

[242] Zhao Y, Jia Y, Wang J, et al. circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis. Mol Cancer. 2024; 23(1): 47.

[243] Xiang T, Chen L, Wang H, et al. The circular RNA circFOXK2 enhances the tumorigenesis of non-small cell lung cancer through the miR-149-3p/IL-6 axis. Biochem Genet. 2024; 62(1): 95-111.

[244] Zhou B, Mo Z, Lai G, et al. Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-?B-IL-6 axis of tumor-associated macrophages. J Exp Clin Cancer Res. 2023; 42(1): 48.

[245] Liotti F, Visciano C, Melillo RM. Inflammation in thyroid oncogenesis. Am J Cancer Res. 2012; 2(3): 286-297.

[246] Xie Z, Li X, He Y, et al. Immune cell confrontation in the papillary thyroid carcinoma microenvironment. Front Endocrinol. 2020; 11: 570604.

[247] Yuan S, Norgard RJ, Stanger BZ. Cellular plasticity in cancer. Cancer Discov. 2019; 9(7): 837-851.

[248] Wang C, Liu Y, Zuo Z, et al. Dual role of exosomal circCMTM3 derived from GSCs in impeding degradation and promoting phosphorylation of STAT5A to facilitate vasculogenic mimicry formation in glioblastoma. Theranostics. 2024; 14(14): 5698-5724.

[249] Zheng S, Hu C, Lin H, et al. circCUL2 induces an inflammatory CAF phenotype in pancreatic ductal adenocarcinoma via the activation of the MyD88-dependent NF-κB signaling pathway. J Exp Clin Cancer Res. 2022; 41(1): 71.

[250] Fumagalli MR, Lionetti MC, Zapperi S, La Porta CAM. Cross-talk between circRNAs and mRNAs modulates MiRNA-mediated circuits and affects melanoma plasticity. Cancer Microenviron. 2019; 12(2-3): 95-104.

[251] Buffet C, Wassermann J, Hecht F, et al. Redifferentiation of radioiodine-refractory thyroid cancers. Endocr Relat Cancer. 2020; 27(5): R113-R132.

[252] Zhang Z, Huang Y, Guo A, Yang L. Research progress of circular RNA molecules in aging and age-related diseases. Ageing Res Rev. 2023; 87: 101913.

[253] Li Y, Fan A, Zhang Y, et al. Cellular senescence: a potential mode of circular RNAs regulating prostate cancer. MedComm—Oncology. 2023; 2(4): e61.

[254] Li Q, Zhao YH, Xu C, et al. Chemotherapy-induced senescence reprogramming promotes nasopharyngeal carcinoma metastasis by circRNA-mediated PKR activation. Adv Sci (Weinh). 2023; 10(8): e2205668.

[255] Chen Z, Zuo X, Pu L, et al. circLARP4 induces cellular senescence through regulating miR-761/RUNX3/p53/p21 signaling in hepatocellular carcinoma. Cancer Sci. 2019; 110(2): 568-581.

[256] Du WW, Yang W, Li X, et al. A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy. Oncogene. 2018; 37(44): 5829-5842.

[257] Wu S, Dai X, Xia Y, et al. Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome. Cell Rep. 2024; 43(4): 114111.

[258] Ding F, Lu L, Wu C, et al. circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR. Theranostics. 2022; 12(17): 7550-7566.. Research Paper.

[259] Wang D, Chen D, Liang L, Hu J. The circZEB1/miR-337-3p/OGT axis mediates angiogenesis and metastasis via O-GlcNAcylation and up-regulating YBX1 in breast cancer. Heliyon. 2024; 10(14): e34079.

[260] Lan J, Wang L, Cao J, Wan Y, Zhou Y. circBRAF promotes the progression of triple-negative breast cancer through modulating methylation by recruiting KDM4B to histone H3K9me3 and IGF2BP3 to mRNA. Am J Cancer Res. 2024; 14(5): 2020-2036.

[261] Li Y, Wang Z, Gao P, et al. CircRHBDD1 promotes immune escape via IGF2BP2/PD-L1 signaling and acts as a nanotherapeutic target in gastric cancer. J Transl Med. 2024; 22(1): 704.

[262] Ma G, Li Y, Meng F, Sui C, Wang Y, Cheng D. Hsa_circ_0000119 promoted ovarian cancer development via enhancing the methylation of CDH13 by sponging miR-142-5p. J Biochem Mol Toxicol. 2023; 37(3): e23264.

[263] He H, Zhang Q, Gu Q, Yang H, Yue C. CircGNAO1 strengthens its host gene GNAO1 expression for suppression of hepatocarcinogenesis. Heliyon. 2024; 10(12): e32848.

[264] Ginsberg SD, Blaser MJ. Alzheimer’s disease has its origins in early life via a perturbed microbiome. J Infect Dis. 2024; 230(Supplement_2): S141-S149.

[265] Abdullah ST, Abdullah SR, Hussen BM, Younis YM, Rasul MF, Taheri M. Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets. Noncoding RNA Res. 2024; 9(1): 236-252.

[266] Zhang Y, Huang R, Cheng M, et al. Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2. Microbiome. 2019; 7(1): 116.

[267] Bokulich NA. Bioinformatics challenges for profiling the microbiome in cancer: pitfalls and opportunities. Trends Microbiol. 2024; 32(12): 1163-1166.

[268] Rahal Z, Liu Y, Peng F, et al. Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment. Cancer Immunol Res. 2024; 12(12): 1736-1752.

[269] Lloyd L. Gut microbiota influence bladder tumour development. Nat Rev Urol. 2024; 21(10): 576.

[270] Guo Y, Zhu X, Zeng M, et al. A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota. Transl Psychiatry. 2021; 11(1): 328.

[271] Zhu Z, Huang J, Li X, et al. Gut microbiota regulate tumor metastasis via circRNA/miRNA networks. Gut Microbes. 2020; 12(1): 1788891.

[272] Guo R, Cui X, Li X, et al. CircMAN1A2 is upregulated by Helicobacter pylori and promotes development of gastric cancer. Cell Death Dis. 2022; 13(4): 409.

[273] Zhao W, Yao Z, Cao J, et al. Helicobacter pylori upregulates circPGD and promotes development of gastric cancer. J Cancer Res Clin Oncol. 2024; 150(2): 104.

[274] Liu Y, Cao J, Yang Q, et al. CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis. Biol Direct. 2023; 18(1): 51.

[275] Shi Z, Li Z, Zhang M. Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies. J Transl Med. 2024; 22(1): 837.

[276] Fedorova M, Snezhkina A, Kalinin D, et al. Intratumoral microbiome in head and neck paragangliomas. Int J Mol Sci. 2024; 25(17): 9180.

[277] Liu Q, Pan LZ, Hu M, Ma JY. Molecular network-based identification of circular RNA-associated ceRNA network in papillary thyroid cancer. Pathol Oncol Res. 2019.

[278] Lou W, Ding B, Wang J, Xu Y. The involvement of the hsa_circ_0088494-miR-876-3p-CTNNB1/CCND1 axis in carcinogenesis and progression of papillary thyroid carcinoma. Front Cell Dev Biol. 2020; 8: 605940.

[279] Guo M, Sun Y, Ding J, et al. Circular RNA profiling reveals a potential role of hsa_circ_IPCEF1 in papillary thyroid carcinoma. Mol Med Rep. 2021; 24(2): 603.

[280] Lv C, Sun W, Huang J, Qin Y, Ji X, Zhang H. Expression profiles of circular RNAs in human papillary thyroid carcinoma based on RNA deep sequencing. Onco Targets Ther. 2021; 14: 3821-3832.

[281] Lan X, Xu J, Chen C, et al. The landscape of circular RNA expression profiles in papillary thyroid carcinoma based on RNA sequencing. Cell Physiol Biochem: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2018; 47(3): 1122-1132.

[282] Guo X, Tan W, Wang C. The emerging roles of exosomal circRNAs in diseases. Clin Transl Oncol. 2020; 23(6): 1020-1033.

[283] Ma Z, Shuai Y, Gao X, Wen X, Ji J. Circular RNAs in the tumour microenvironment. Mol Cancer. 2020; 19(1): 8.

[284] Dai W, Jin X, Han L, et al. Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma. Cell Death Dis. 2020; 11(9): 743.

[285] Hardin H, Helein H, Meyer K, et al. Thyroid cancer stem-like cell exosomes: regulation of EMT via transfer of lncRNAs. Lab Invest. 2018; 98(9): 1133-1142.

[286] Ye W, Deng X, Fan Y. Exosomal miRNA423-5p mediated oncogene activity in papillary thyroid carcinoma: a potential diagnostic and biological target for cancer therapy. Neoplasma. 2019; 66(4): 516-523.

[287] Yang C, Wei Y, Yu L, Xiao Y. Identification of altered circular RNA Expression in serum exosomes from patients with papillary thyroid carcinoma by high-throughput sequencing. Med Sci Monit: International Medical Journal of Experimental and Clinical Research. 2019; 25: 2785-2791.

[288] Lin Q, Qi Q, Hou S, et al. Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis. Bioengineered. 2021; 12(2): 10136-10149.

[289] Wang Y, Zhang J, Yang Y, et al. Circular RNAs in human diseases. MedComm. 2024; 5(9): e699.

[290] Guo Y, Huang Q, Zheng J, et al. Diagnostic significance of downregulated circMORC3 as a molecular biomarker of hypopharyngeal squamous cell carcinoma: a pilot study. Cancer Manag Res. 2020; 12: 43-49.

[291] Zhang Y, Li J, Cui Q, Hu P, Hu S, Qian Y. Circular RNA hsa_circ_0006091 as a novel biomarker for hepatocellular carcinoma. Bioengineered. 2022; 13(2): 1988-2003.

[292] Guo Y, Huang Q, Zheng J, et al. Diagnostic role of dysregulated circular RNA hsa_circ_0036722 in laryngeal squamous cell carcinoma. Onco Targets Ther. 2020; 13: 5709-5719.

[293] Zong L, Sun Q, Zhang H, et al. Increased expression of circRNA_102231 in lung cancer and its clinical significance. Biomed Pharmacother. 2018; 102: 639-644.

[294] Wang C, Tan S, Liu WR, et al. RNA-Seq profiling of circular RNA in human lung adenocarcinoma and squamous cell carcinoma. Mol Cancer. 2019; 18(1): 134.

[295] Sun XH, Wang YT, Li GF, Zhang N, Fan L. Serum-derived three-circRNA signature as a diagnostic biomarker for hepatocellular carcinoma. Cancer Cell Int. 2020; 20: 226.

[296] Liu M, Lai M, Li D, et al. Nucleus-localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription. Cancer Sci. 2023; 114(10): 3884-3899.

[297] Lai M, Liu M, Li D, et al. circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression. iScience. 2023; 26(10): 107818.

[298] Zhang Q, Qin S, Peng C, Liu Y, Huang Y, Ju S. Circulating circular RNA hsa_circ_0023179 acts as a diagnostic biomarker for non-small-cell lung cancer detection. J Cancer Res Clin Oncol. 2023; 149(7): 3649-3660.

[299] Cui Y, Wu X, Jin J, et al. CircHERC1 promotes non-small cell lung cancer cell progression by sequestering FOXO1 in the cytoplasm and regulating the miR-142-3p-HMGB1 axis. Mol Cancer. 2023; 22(1): 179.

[300] Song Z, Zhang Q, Zhu J, Yin G, Lin L, Liang C. Identification of urinary hsa_circ _0137439 as potential biomarker and tumor regulator of bladder cancer. Neoplasma. 2020; 67(1): 137-146.

[301] Yang Y, Li J, Yao W, Zou G, Ye X, Mo Q. Diagnostic value of urine cyclic RNA-0071196 for bladder urothelial carcinoma. BMC Urol. 2024; 24(1): 88.

[302] Zhao SY, Wang J, Ouyang SB, Huang ZK, Liao L. Salivary circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as novel biomarkers for the diagnosis of oral squamous cell carcinoma. Cell Physiol Biochem: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2018; 47(6): 2511-2521.

[303] Guo D, Li F, Zhao X, et al. Circular RNA expression and association with the clinicopathological characteristics in papillary thyroid carcinoma. Oncol Rep. 2020; 44(2): 519-532.

[304] Du G, Ma R, Li H, et al. Increased expression of hsa_circ_0002111 and its clinical significance in papillary thyroid cancer. Front Oncol. 2021; 11: 644011.

[305] Lan X, Cao J, Xu J, et al. Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma. J Clin Lab Anal. 2018; 32(8): e22573.

[306] Ding H, Wang X, Liu H, Na L. Higher circular RNA_0015278 correlates with absence of extrathyroidal invasion, lower pathological tumor stages, and prolonged disease-free survival in papillary thyroid carcinoma patients. J Clin Lab Anal. 2021; 35(7): e23819.

[307] Fan CM, Wang JP, Tang YY, et al. circMAN1A2 could serve as a novel serum biomarker for malignant tumors. Cancer Sci. 2019; 110(7): 2180-2188.

[308] Shi E, Ye J, Zhang R, et al. A combination of circRNAs as a diagnostic tool for discrimination of papillary thyroid cancer. Onco Targets Ther. 2020; 13: 4365-4372.

[309] Sun JW, Qiu S, Yang JY, Chen X, Li HX. Hsa_circ_0124055 and hsa_circ_0101622 regulate proliferation and apoptosis in thyroid cancer and serve as prognostic and diagnostic indicators. Eur Rev Med Pharmacol Sci. 2020; 24(8): 4348-4360.

[310] Yu W, Ma B, Zhao W, et al. The combination of circRNA-UMAD1 and Galectin-3 in peripheral circulation is a co-biomarker for predicting lymph node metastasis of thyroid carcinoma. Am J Transl Res. 2020; 12(9): 5399-5415.

[311] Yang W, Bai C, Zhang L, et al. Correlation between serum circRNA and thyroid micropapillary carcinoma with cervical lymph node metastasis. Medicine (Baltimore). 2020; 99(47): e23255.

[312] Chen C, Duckworth CA, Zhao Q, Pritchard DM, Rhodes JM, Yu LG. Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium. Clin Cancer Res. 2013; 19(7): 1693-1704.

[313] Tian J, Xi X, Wang J, et al. CircRNA hsa_circ_0004585 as a potential biomarker for colorectal cancer. Cancer Manag Res. 2019; 11: 5413-5423.

[314] Wang Z, Yang L, Wu P, et al. The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin. Mol Cancer. 2022; 21(1): 29.

[315] Ling Y, Liang G, Lin Q, et al. circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer. Mol Cancer. 2022; 21(1): 8.

[316] Meng H, Li R, Xie Y, et al. Nanoparticles mediated circROBO1 silencing to inhibit hepatocellular carcinoma progression by modulating miR-130a-5p/CCNT2 axis. Int J Nanomedicine. 2023; 18: 1677-1693.

[317] Papatsirou M, Kontos CK, Ntanasis-Stathopoulos I, et al. Exploring the molecular biomarker utility of circCCT3 in multiple myeloma: a favorable prognostic indicator, particularly for R-ISS II patients. Hemasphere. 2024; 8(1): e34.

[318] Papatsirou M, Kontos CK, Ntanasis-Stathopoulos I, et al. ciRS-7 circular RNA overexpression in plasma cells is a promising molecular biomarker of unfavorable prognosis in multiple myeloma. EJHaem. 2024; 5(4): 677-689.

[319] Luo Y, Liu F, Gui R. High expression of circulating exosomal circAKT3 is associated with higher recurrence in HCC patients undergoing surgical treatment. Surg Oncol. 2020; 33: 276-281.

[320] Xing L, Xia M, Jiao X, Fan L. Hsa_circ_0004831 serves as a blood-based prognostic biomarker for colorectal cancer and its potentially circRNA-miRNA-mRNA regulatory network construction. Cancer Cell Int. 2020; 20(1): 557.

[321] Mai S, Zhang Z, Mi W. Upregulation of circ_PVT1 and circ_001569 indicate unfavorable prognosis in colorectal cancer. Ann Clin Lab Sci. 2021; 51(1): 55-60.

[322] Yan L, Yan Q. Serum circRNA_100199 is a prognostic biomarker in acute myeloid leukemia. Int J Gen Med. 2023; 16: 4661-4668.

[323] Xie H, Yao J, Wang Y, Ni B. Exosome-transmitted circVMP1 facilitates the progression and cisplatin resistance of non-small cell lung cancer by targeting miR-524-5p-METTL3/SOX2 axis. Drug Deliv. 2022; 29(1): 1257-1271.

[324] Chen X, Chen RX, Wei WS, et al. PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res. 2018; 24(24): 6319-6330.

[325] Chen QW, Wang DQ, Ding BX, et al. [hsa_circ_0000231 affects the progression of tongue squamous cell carcinoma by activating Wnt/β-catenin signaling pathway]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022; 57(10): 1230-1239.

[326] Long F, Lin Z, Li L, et al. Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer. Mol Cancer. 2021; 20(1): 26.

[327] Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024; 4(1): 47-53.

[328] Zeng H, Zheng R, Sun K, et al. Cancer survival statistics in China 2019–2021: a multicenter, population-based study. J Natl Cancer Cent. 2024; 4(3): 203-213.

[329] Cao X, Hou J, An Q, Assaraf YG, Wang X. Towards the overcoming of anticancer drug resistance mediated by p53 mutations. Drug Resist Updat: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy. 2020; 49: 100671.

[330] Saxena M, Stephens MA, Pathak H, Rangarajan A. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis. 2011; 2(7): e179.

[331] Li Y, Wang Z, Ajani JA, Song S. Drug resistance and Cancer stem cells. Cell Commun Signal. 2021; 19(1): 19.

[332] Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4): 275-284.

[333] Cui C, Yang J, Li X, Liu D, Fu L, Wang X. Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance. Mol Cancer. 2020; 19(1): 58.

[334] Lu L, Gao Z, Jin L, Geng H, Liang Z. Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy. Front Pharmacol. 2024; 15: 1435264.

[335] Kunická T, Souček P. Importance of ABCC1 for cancer therapy and prognosis. Drug Metab Rev. 2014; 46(3): 325-342.

[336] Wang X, Wang H, Jiang H, Qiao L, Guo C. Circular RNAcirc_0076305 promotes cisplatin (DDP) resistance of non-small cell lung cancer cells by regulating ABCC1 through miR-186-5p. Cancer Biother Radiopharm. 2023; 38(5): 293-304.

[337] Zheng F, Xu R. CircPVT1 contributes to chemotherapy resistance of lung adenocarcinoma through miR-145-5p/ABCC1 axis. Biomed Pharmacother. 2020; 124: 109828.

[338] Qu B, Liu J, Peng Z, et al. Macrophages enhance cisplatin resistance in gastric cancer through the transfer of circTEX2. J Cell Mol Med. 2024; 28(5): e18070.

[339] Huang C, Qin L, Chen S, Huang Q. CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression. Anticancer Drugs. 2023; 34(3): 395-404.

[340] Wei W, Liu K, Huang X, et al. EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance. J Exp Clin Cancer Res. 2024; 43(1): 2.

[341] Zou Y, Yang A, Chen B, et al. crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer. Drug Resist Updat: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy. 2024; 77: 101126.

[342] Chen Z, Xu Z, Wang Q, et al. Exosome-delivered circRNA circSYT15 contributes to cisplatin resistance in cervical cancer cells through the miR-503-5p/RSF1 axis. Cell Cycle. 2023; 22(20): 2211-2228.

[343] Meng X, Xiao W, Sun J, et al. CircPTK2/PABPC1/SETDB1 axis promotes EMT-mediated tumor metastasis and gemcitabine resistance in bladder cancer. Cancer Lett. 2023; 554: 216023.

[344] Xia W, Chen W, Ni C, et al. Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway. Breast Cancer Res. 2023; 25(1): 85.

[345] Cheng X, Yang H, Chen Y, et al. METTL3-mediated m(6)A modification of circGLIS3 promotes prostate cancer progression and represents a potential target for ARSI therapy. Cell Mol Biol Lett. 2024; 29(1): 109.

[346] Cheng Y, Zhu Y, Xiao M, et al. circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53. Cell Oncol. 2023; 46(3): 677-695.

[347] Zhu Y, Liang L, Zhao Y, et al. CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination. J Nanobiotechnology. 2024; 22(1): 35.

[348] Liang X, Liu X, Song Z, Zhu J, Zhang J. Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p. Clin Exp Pharmacol Physiol. 2022; 49(12): 1257-1269.

[349] Li H, Luo F, Jiang X, et al. CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype. J Immunother Cancer. 2022; 10(3): e004029.

[350] Hu C, Xia R, Zhang X, et al. circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis. Mol Cancer. 2022; 21(1): 24.

[351] Hong W, Xue M, Jiang J, Zhang Y, Gao X. Circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC). J Exp Clin Cancer Res. 2020; 39(1): 149.

[352] Zhang X, Yang J. Role of non-coding RNAs on the radiotherapy sensitivity and resistance of head and neck cancer: from basic research to clinical application. Front Cell Dev Biol. 2020; 8: 637435.

[353] Ju Z, Lei M, Xuan L, et al. P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex. J Adv Res. 2023.

[354] He Y, Zheng L, Yuan M, et al. Exosomal circPRRX1 functions as a ceRNA for miR-596 to promote the proliferation, migration, invasion, and reduce radiation sensitivity of gastric cancer cells via the upregulation of NF-κB activating protein. Anticancer Drugs. 2022; 33(10): 1114-1125.

[355] Lin C, Huang X, Qian Y, Li J, He Y, Su H. CircRNA_101491 regulated the radiation sensitivity of esophageal squamous cell carcinomas via sponging miR-125a-5p. Radiat Oncol. 2024; 19(1): 84.

[356] Zhang C, Wang J, Wang H, Li J. Circ-ABCC1 enhances radioresistance of breast cancer cells via miR-627-5p/ABCC1 axis. Cell Mol Biol (Noisy-le-grand). 2022; 68(10): 187-192.

[357] Zhou X, Yuan G, Wu Y, Yan S, Jiang Q, Tang S. EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma. Cell Mol Life Sci. 2022; 79(7): 357.

[358] Qu H, Wang Y, Yan Q, et al. CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair. J Exp Clin Cancer Res. 2024; 43(1): 122.

[359] Hu P, Lin L, Huang T, et al. Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis. Cancer Cell Int. 2023; 23(1): 308.

[360] Wang X, Zheng D, Wang C, Chen W. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis. Open Med (Wars). 2023; 18(1): 20230678.

[361] Wang P, Sun Y, Yang Y, Chen Y, Liu H. Circ_0067835 knockdown enhances the radiosensitivity of colorectal cancer by miR-296-5p/IGF1R axis. Onco Targets Ther. 2021; 14: 491-502.

[362] Oh SW, Moon SH, Park DJ, et al. Combined therapy with 131I and retinoic acid in Korean patients with radioiodine-refractory papillary thyroid cancer. Eur J Nucl Med Mol Imaging. 2011; 38(10): 1798-1805.

[363] Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006; 91(8): 2892-2899.

[364] Chen F, Yin S, Feng Z, et al. Knockdown of circ_NEK6 decreased (131)I resistance of differentiated thyroid carcinoma via regulating miR-370-3p/MYH9 axis. Technol Cancer Res Treat. 2021; 20: 15330338211004950.

[365] Chen F, Feng Z, Zhu J, et al. Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway. Cancer Biol Ther. 2018; 19(12): 1139-1152.

[366] Pan Z, Cai J, Lin J, et al. A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer. Mol Cancer. 2020; 19(1): 71.

[367] Chen C, Liu Q, Wang J, et al. Circulating circular RNAs as novel biomarkers and functional prediction for the early diagnosis in post-stroke cognitive impairment: a single-center prospective study in China. J Stroke Cerebrovasc Dis. 2024; 33(11): 107945.

[368] Yuan C, Xu Y, Zhou L, et al. Value of CDR1-AS as a predictive and prognostic biomarker for patients with breast cancer receiving neoadjuvant chemotherapy in a prospective Chinese cohort. Eur J Med Res. 2024; 29(1): 454.

[369] Feng X-Y, Zhu S-X, Pu K-J, Huang H-J, Chen Y-Q, Wang W-T. New insight into circRNAs: characterization, strategies, and biomedical applications. Exp Hematol Oncol. 2023; 12(1): 91.

[370] Jost I, Shalamova LA, Gerresheim GK, Niepmann M, Bindereif A, Rossbach O. Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges. RNA Biology. 2018; 15(8): 1032-1039.

[371] Liu X, Abraham JM, Cheng Y, et al. Synthetic circular RNA functions as a miR-21 sponge to suppress gastric carcinoma cell proliferation. Mol Ther Nucleic Acids. 2018; 13: 312-321.

[372] Chen R, Wang SK, Belk JA, et al. Engineering circular RNA for enhanced protein production. Nat Biotechnol. 2022.

[373] Obi P, Chen YG. The design and synthesis of circular RNAs. Methods. 2021; 196: 85-103.

[374] Pfafenrot C, Schneider T, Müller C, et al. Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs. Nucleic Acids Res. 2021; 49(21): 12502-12516.

[375] Su P, Zhang L, Zhou F, Zhang L. Circular RNA vaccine, a novel mRNA vaccine design strategy for SARS-CoV-2 and variants. MedComm. 2022; 3(3): e153.

[376] Rama AR, Quiñonero F, Mesas C, Melguizo C, Prados J. Synthetic circular miR-21 sponge as tool for lung cancer treatment. Int J Mol Sci. 2022; 23(6): 2963.

[377] Kasamatsu A, Nozaki R, Kawasaki K, et al. Synthetic circular RNA for microRNA-1269a suppresses tumor progression in oral squamous cell carcinoma. Cancers. 2024; 16(6): 1242.

[378] Wang Z, Ma K, Cheng Y, et al. Synthetic circular multi-miR sponge simultaneously inhibits miR-21 and miR-93 in esophageal carcinoma. Lab Invest. 2019; 99(10): 1442-1453.

[379] Bayat H, Pourgholami MH, Rahmani S, Pournajaf S, Mowla SJ. Synthetic miR-21 decoy circularized by tRNA splicing mechanism inhibited tumorigenesis in glioblastoma in vitro and in vivo models. Mol Ther Nucleic Acids. 2023; 32: 432-444.

[380] Adibzadeh S, Amiri S, Barkhordari F, et al. CHO cell engineering via targeted integration of circular miR-21 decoy using CRISPR/RMCE hybrid system. Appl Microbiol Biotechnol. 2024; 108(1): 434.

[381] Chen R, Wang SK, Belk JA, et al. Engineering circular RNA for enhanced protein production. Nat Biotechnol. 2023; 41(2): 262-272.

[382] Kameda S, Ohno H, Saito H. Synthetic circular RNA switches and circuits that control protein expression in mammalian cells. Nucleic Acids Res. 2023; 51(4): e24.

[383] Wang X, Zhang H, Yang H, et al. Exosome-delivered circRNA promotes glycolysis to induce chemoresistance through the miR-122-PKM2 axis in colorectal cancer. Mol Oncol. 2020; 14(3): 539-555.

[384] Yang H, Li X, Meng Q, et al. CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer. Mol Cancer. 2020; 19(1): 13.

[385] Jahns H, Degaonkar R, Podbevsek P, et al. Small circular interfering RNAs (sciRNAs) as a potent therapeutic platform for gene-silencing. Nucleic Acids Res. 2021; 49(18): 10250-10264.

[386] Zhang L, Liang D, Wang Y, et al. Caged circular siRNAs for photomodulation of gene expression in cells and mice. Chem Sci. 2018; 9(1): 44-51.

[387] Hama Faraj GS, Hussen BM, Abdullah SR, et al. Advanced approaches of the use of circRNAs as a replacement for cancer therapy. Noncoding RNA Res. 2024; 9(3): 811-830.

[388] Choi SW, Nam JW. Optimal design of synthetic circular RNAs. Exp Mol Med. 2024; 56(6): 1281-1292.

[389] Loan Young T, Chang Wang K, James Varley A, Li B. Clinical delivery of circular RNA: lessons learned from RNA drug development. Adv Drug Deliv Rev. 2023; 197: 114826.

[390] Tang T, Chen L, Zhang M, et al. Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery. Diabetol Metab Syndr. 2024; 16(1): 37.

[391] Muskan M, Abeysinghe P, Cecchin R, Branscome H, Morris KV, Kashanchi F. Therapeutic potential of RNA-enriched extracellular vesicles: the next generation in RNA delivery via biogenic nanoparticles. Mol Ther. 2024; 32(9): 2939-2949.

[392] Huang Q, Chu Z, Wang Z, et al. circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models. Nat Commun. 2024; 15(1): 3904.

[393] Zhou Q, Fang L, Tang Y, et al. Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer. J Cancer. 2024; 15(6): 1770-1778.

[394] Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Mol Cancer. 2022; 21(1): 179.

[395] Yao X, Mao Y, Wu D, et al. Exosomal circ_0030167 derived from BM-MSCs inhibits the invasion, migration, proliferation and stemness of pancreatic cancer cells by sponging miR-338-5p and targeting the Wif1/Wnt8/β-catenin axis. Cancer Lett. 2021; 512: 38-50.

[396] Yuan Z, Xiong B, Liu L, et al. Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1. J Biochem Mol Toxicol. 2024; 38(2): e23656.

[397] Li X, Peng X, Zoulikha M, et al. Multifunctional nanoparticle-mediated combining therapy for human diseases. Signal Transduct Target Ther. 2024; 9(1): 1.

[398] Racca L, Liuzzi E, Comparato S, Giordano G, Pignochino Y. Nanoparticles-delivered circular RNA strategy as a novel antitumor approach. Int J Mol Sci. 2024; 25(16): 8934.

[399] Sell M, Lopes AR, Escudeiro M, et al. Application of nanoparticles in cancer treatment: a concise review. Nanomaterials. 2023; 13(21): 2887.

[400] Tran S, DeGiovanni P-J, Piel B, Rai P. Cancer nanomedicine: a review of recent success in drug delivery. Clin Transl Med. 2017; 6(1): e44.

[401] Wu M, Lin X, Tan X, et al. Photoresponsive nanovehicle for two independent wavelength light-triggered sequential release of P-gp shRNA and doxorubicin to optimize and enhance synergistic therapy of multidrug-resistant cancer. ACS Appl Mater Interfaces. 2018; 10(23): 19416-19427.

[402] Yi Z, Li Y, Wu Y, et al. Circular RNA 0001073 attenuates malignant biological behaviours in breast cancer cell and is delivered by nanoparticles to inhibit mice tumour growth. Onco Targets Ther. 2020; 13: 6157-6169.

[403] Müller S, Wedler A, Breuer J, et al. Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice. NAR Cancer. 2020; 2(3): zcaa014.

[404] Lavenniah A, Luu TDA, Li YP, et al. Engineered circular RNA sponges act as miRNA inhibitors to attenuate pressure overload-induced cardiac hypertrophy. Mol Ther. 2020; 28(6): 1506-1517.

[405] Rossbach O. Artificial circular RNA sponges targeting microRNAs as a novel tool in molecular biology. Mol Ther Nucleic Acids. 2019; 17: 452-454.

[406] Qi Y, Han W, Chen D, et al. Engineering circular RNA regulators to specifically promote circular RNA production. Theranostics. 2021; 11(15): 7322-7336.

[407] Sun YJ, Chen WD, Liu J, et al. A conformational restriction strategy for the control of CRISPR/Cas gene editing with photoactivatable guide RNAs. Angew Chem Int Ed Engl. 2023; 62(5): e202212413.

[408] Zhang L, Cao S-M, Wu H, Yan M, Li J, Chen L-L. A CRISPR/RfxCas13d-mediated strategy for efficient RNA knockdown in mouse embryonic development. Sci China Life Sci. 2024; 67(11): 2297-2306.

[409] Niu D, Wu Y, Lian J. Circular RNA vaccine in disease prevention and treatment. Signal Transduct Target Ther. 2023; 8(1): 341.

[410] Cui J, Zhang L, Zhang Z, et al. A precise and efficient circular RNA synthesis system based on a ribozyme derived from Tetrahymena thermophila. Nucleic Acids Res. 2023; 51(14): e78.

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