Non-coding RNA and drug resistance in head and neck cancer

Abstract

Head and neck cancer (HNC) is ranked as the sixth most common malignant tumor, and the overall survival rate with current treatment options remains concerning, primarily due to drug resistance that develops following antitumor therapy. Recent studies indicate that non-coding RNAs play a crucial role in drug resistance among HNC patients. This article systematically reviews the current research landscape, explores novel targets and treatment strategies related to non-coding RNAs and HNC resistance, raises some unresolved issues, and discusses five promising research directions in this field: ferroptosis, nanomedicine, exosomes, proteolysis-targeting chimeras (PROTACs), and artificial intelligence. We hope that our work will contribute to advancing research on overcoming HNC resistance through the regulation of non-coding RNAs.

Keywords

Head and neck cancer / non-coding RNA / microRNA / long non-coding RNA / circular RNA / drug resistance

References

[1] Li Q,Alu A,Shi H.Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal Transduct Target Ther2023;8:31 PMCID:PMC9842704

[2] Pfister DG,Adelstein D.Head and neck cancers, version 2.2020, NCCN clinical practice guidelines in oncology.J Natl Compr Canc Netw2020;18:873-98

[3] Mody MD,Yom SS,Saba NF.Head and neck cancer.Lancet2021;398:2289-99

[4] Chow LQM.Head and neck cancer.N Engl J Med2020;382:60-72

[5] Wong KCW,Lo KW.Nasopharyngeal carcinoma: an evolving paradigm.Nat Rev Clin Oncol2021;18:679-95

[6] Leemans CR,Brakenhoff RH.The molecular biology of head and neck cancer.Nat Rev Cancer2011;11:9-22

[7] Dai F,Zheng X.Non-coding RNAs in drug resistance of head and neck cancers: a review.Biomed Pharmacother2020;127:110231

[8] Romano G,Acunzo M.Small non-coding RNA and cancer.Carcinogenesis2017;38:485-91 PMCID:PMC6248440

[9] Nemeth K,Ferracin M.Non-coding RNAs in disease: from mechanisms to therapeutics.Nat Rev Genet2024;25:211-32

[10] Patop IL,Kadener S.Past, present, and future of circRNAs.EMBO J2019;38:e100836 PMCID:PMC6694216

[11] Kabekkodu SP,Varghese VK,Chakrabarty S.Clustered miRNAs and their role in biological functions and diseases.Biol Rev Camb Philos Soc2018;93:1955-86

[12] Ransohoff JD,Khavari PA.The functions and unique features of long intergenic non-coding RNA.Nat Rev Mol Cell Biol2018;19:143-57 PMCID:PMC5889127

[13] Kristensen LS,Hager H.The emerging roles of circRNAs in cancer and oncology.Nat Rev Clin Oncol2022;19:188-206

[14] Wen SY,Yang BB.Circular RNA translation: novel protein isoforms and clinical significance.Trends Mol Med2022;28:405-20

[15] Williams M,Phimmachanh M,van Zandwijk N.Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways.Cancer Drug Resist2019;2:1193-206 PMCID:PMC9019216

[16] Chen B,Yang C,Horst D.Targeting non-coding RNAs to overcome cancer therapy resistance.Signal Transduct Target Ther2022;7:121 PMCID:PMC9008121

[17] Zhang X,Zhou H.Role of non-coding RNAs and RNA modifiers in cancer therapy resistance.Mol Cancer2020;19:47 PMCID:PMC7050132

[18] Mattick JS,Carninci P.Long non-coding RNAs: definitions, functions, challenges and recommendations.Nat Rev Mol Cell Biol2023;24:430-47 PMCID:PMC10213152

[19] Huarte M.The emerging role of lncRNAs in cancer.Nat Med2015;21:1253-61

[20] Yuan JH,Wang F.A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma.Cancer Cell2014;25:666-81

[21] Winkle M,Fabbri M.Noncoding RNA therapeutics - challenges and potential solutions.Nat Rev Drug Discov2021;20:629-51 PMCID:PMC8212082

[22] Slack FJ.The role of non-coding RNAs in oncology.Cell2019;179:1033-55 PMCID:PMC7347159

[23] Calin GA.MicroRNA signatures in human cancers.Nat Rev Cancer2006;6:857-66

[24] Cavaliere AF,Zaami S.Towards personalized medicine: non-coding RNAs and endometrial cancer.Healthcare2021;9:965 PMCID:PMC8393611

[25] Piergentili R,Nocella C.Using ncRNAs as tools in cancer diagnosis and treatment-the way towards personalized medicine to improve patients’ health.Int J Mol Sci2022;23:9353 PMCID:PMC9409241

[26] Rupaimoole R.MicroRNA therapeutics: towards a new era for the management of cancer and other diseases.Nat Rev Drug Discov2017;16:203-22

[27] Naorem LD,Muthaiyan M.Comprehensive analysis of dysregulated lncRNAs and their competing endogenous RNA network in triple-negative breast cancer.Int J Biol Macromol2020;145:429-36

[28] Mahato RK,Khullar N.Targeting long non-coding RNAs in cancer therapy using CRISPR-Cas9 technology: a novel paradigm for precision oncology.J Biotechnol2024;379:98-119

[29] Kilikevicius A,Corey DR.Reexamining assumptions about miRNA-guided gene silencing.Nucleic Acids Res2022;50:617-34 PMCID:PMC8789053

[30] Shang R,Senavirathne G.microRNAs in action: biogenesis, function and regulation.Nat Rev Genet2023;24:816-33 PMCID:PMC11087887

[31] Agbu P.MicroRNA-mediated regulation of glucose and lipid metabolism.Nat Rev Mol Cell Biol2021;22:425-38 PMCID:PMC8853826

[32] He B,Cai Q.miRNA-based biomarkers, therapies, and resistance in Cancer.Int J Biol Sci2020;16:2628-47 PMCID:PMC7415433

[33] Pan G,Shang L,Yang S.EMT-associated microRNAs and their roles in cancer stemness and drug resistance.Cancer Commun2021;41:199-217 PMCID:PMC7968884

[34] Meng X,Yang WY.The role of non-coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential.Cancer Commun2021;41:981-1006 PMCID:PMC8504146

[35] Zhang S,Zhao Q,Wu L.Downregulation of long noncoding RNA HCP5/miR-216a-5p/ZEB1 axis inhibits the malignant biological function of laryngeal squamous cell carcinoma cells.Front Immunol2022;13:1022677 PMCID:PMC9561619

[36] Gao F,Wang Y,Luo W.Circ_0109291 promotes cisplatin resistance of oral squamous cell carcinoma by sponging miR-188-3p to increase ABCB1 expression.Cancer Biother Radiopharm2022;37:233-45

[37] Cao W,Liu L.HOTAIR mediates cisplatin resistance in nasopharyngeal carcinoma by regulating miR-106a-5p/SOX4 axis.Bioengineered2022;13:6567-78 PMCID:PMC8975274

[38] Cui J,Zhang X,Zhang J.Exosomal miR-200c suppresses chemoresistance of docetaxel in tongue squamous cell carcinoma by suppressing TUBB3 and PPP2R1B.Aging2020;12:6756-73 PMCID:PMC7202518

[39] Proença C,Ribeiro D,Fernandes E.The role of flavonoids in the regulation of epithelial-mesenchymal transition in cancer: a review on targeting signaling pathways and metastasis.Med Res Rev2023;43:1878-945

[40] Garinet S,Denize T.Clinical assessment of the miR-34, miR-200, ZEB1 and SNAIL EMT regulation hub underlines the differential prognostic value of EMT miRs to drive mesenchymal transition and prognosis in resected NSCLC.Br J Cancer2021;125:1544-51 PMCID:PMC8609001

[41] Chien CS,Chu PY.Lin28B/Let-7 regulates expression of Oct4 and Sox2 and reprograms oral squamous cell carcinoma cells to a stem-like state.Cancer Res2015;75:2553-65

[42] Manikandan M,Arunkumar G.Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism.Mol Cancer2016;15:28 PMCID:PMC4823852

[43] Yang J,Wang WJ.A novel miR-200c/c-myc negative regulatory feedback loop is essential to the EMT process, CSC biology and drug sensitivity in nasopharyngeal cancer.Exp Cell Res2020;391:111817

[44] Deng X,Liu X.miR-296-3p negatively regulated by nicotine stimulates cytoplasmic translocation of c-Myc via MK2 to suppress chemotherapy resistance.Mol Ther2018;26:1066-81 PMCID:PMC6079479

[45] Huni KC,Sullivan M,Howard KM.Chemotherapeutic drug resistance associated with differential miRNA expression of miR-375 and miR-27 among oral cancer cell lines.Int J Mol Sci2023;24:1244 PMCID:PMC9865318

[46] Shaw P,Senthilnathan R.Clinical theragnostic relationship between chemotherapeutic resistance, and sensitivity and miRNA expressions in head and neck cancers: a systematic review and meta-analysis protocol.Genes2021;12:2029 PMCID:PMC8702026

[47] Li T,Li W.MicroRNA-101-3p inhibits nasopharyngeal carcinoma cell proliferation and cisplatin resistance through ZIC5 down-regulation by targeting SOX2.Biol Chem2023;404:961-75

[48] Chen L,Zhao J.H19/miR-107/HMGB1 axis sensitizes laryngeal squamous cell carcinoma to cisplatin by suppressing autophagy in vitro and in vivo.Cell Biol Int2021;45:674-85

[49] Sayyed AA,Mali M.MiR-155 inhibitor-laden exosomes reverse resistance to cisplatin in a 3D tumor spheroid and xenograft model of oral cancer.Mol Pharm2021;18:3010-25

[50] Yang Y,Li M,Wang S.miR-214 modulates the growth and migration of oral cancer before and after chemotherapy through mediating ULK1.J Immunol Res2022;2022:4589182 PMCID:PMC9184158

[51] Wenhao R,Shaoming L,Ling G.circAP1M2 activates ATG9A-associated autophagy by inhibiting miR-1249-3p to promote cisplatin resistance in oral squamous cell carcinoma.J Cell Physiol2023;238:2612-24

[52] Zhao Y,Wu Q.miR-1278 sensitizes nasopharyngeal carcinoma cells to cisplatin and suppresses autophagy via targeting ATG2B.Mol Cell Probes2020;53:101597

[53] Fan S,Chen W.Mitochondrial miRNA determines chemoresistance by reprogramming metabolism and regulating mitochondrial transcription.Cancer Res2019;79:1069-84 PMCID:PMC8631248

[54] Chen W,Lu Y.Decreased expression of mitochondrial miR-5787 contributes to chemoresistance by reprogramming glucose metabolism and inhibiting MT-CO3 translation.Theranostics2019;9:5739-54 PMCID:PMC6735381

[55] Mortezagholi B,Movahed E.MiR-34 by targeting p53 induces apoptosis and DNA damage in paclitaxel-resistant human oral squamous carcinoma cells.Chem Biol Drug Des2023;102:285-91

[56] Nakashima C,Mori S.An axis between the long non-coding RNA HOXA11-AS and NQOs enhances metastatic ability in oral squamous cell carcinoma.Int J Mol Sci2022;23:10704 PMCID:PMC9506332

[57] Kang SH,Lee KY.Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.Theranostics2024;14:460-79 PMCID:PMC10758057

[58] Li P,Liu H.MiR-194 functions as a tumor suppressor in laryngeal squamous cell carcinoma by targeting Wee1.J Hematol Oncol2017;10:32 PMCID:PMC5264457

[59] Luo X,Hua Z.Exosomes-mediated tumor metastasis through reshaping tumor microenvironment and distant niche.J Control Release2023;353:327-36

[60] Dai J,Zhong S.Exosomes: key players in cancer and potential therapeutic strategy.Signal Transduct Target Ther2020;5:145 PMCID:PMC7406508

[61] Huang C,Feng X,Li Y.Delivery of engineered primary tumor-derived exosomes effectively suppressed the colorectal cancer chemoresistance and liver metastasis.ACS Nano2023;17:10313-26

[62] Qin X,Wang X.Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5.Genome Biol2019;20:12 PMCID:PMC6332863

[63] Li J,Chao H.Exosomal transfer of miR-106a-5p contributes to cisplatin resistance and tumorigenesis in nasopharyngeal carcinoma.J Cell Mol Med2021;25:9183-98 PMCID:PMC8500979

[64] Babaei G,Jaghi NZZ.EMT, cancer stem cells and autophagy; The three main axes of metastasis.Biomed Pharmacother2021;133:110909

[65] Rao X,Luo H.Targeting gastric cancer stem cells to enhance treatment response.Cells2022;11:2828 PMCID:PMC9496718

[66] Lu H,Yang GD.Targeting cancer stem cell signature gene SMOC-2 Overcomes chemoresistance and inhibits cell proliferation of endometrial carcinoma.EBioMedicine2019;40:276-89 PMCID:PMC6412073

[67] Jang TH,Tung SL.MicroRNA-485-5p targets keratin 17 to regulate oral cancer stemness and chemoresistance via the integrin/FAK/Src/ERK/β-catenin pathway.J Biomed Sci2022;29:42 PMCID:PMC9202219

[68] Lin SC,Yeh LY,Kao SY.Activation of the miR-371/372/373 miRNA cluster enhances oncogenicity and drug resistance in oral carcinoma cells.Int J Mol Sci2020;21:9442 PMCID:PMC7764723

[69] Cai L,Chong T.EBV-miR-BART7-3p imposes stemness in nasopharyngeal carcinoma cells by suppressing SMAD7.Front Genet2019;10:939 PMCID:PMC6811651

[70] Zhang P,Shi Z.miR-205-5p regulates epithelial-mesenchymal transition by targeting PTEN via PI3K/AKT signaling pathway in cisplatin-resistant nasopharyngeal carcinoma cells.Gene2019;710:103-13

[71] Gu J,Sun L,Jiang XJ.miR-552 promotes laryngocarcinoma cells proliferation and metastasis by targeting p53 pathway.Cell Cycle2020;19:1012-21 PMCID:PMC7217371

[72] Sheng S,Mao D.MicroRNA-21 induces cisplatin resistance in head and neck squamous cell carcinoma.PLoS One2022;17:e0267017 PMCID:PMC9009694

[73] Wu R,Liu H.MicroRNA-577/EIF5A2 axis suppressed the proliferation of DDP-resistant nasopharyngeal carcinoma cells by blocking TGF-β signaling pathway.Chem Biol Drug Des2023;102:815-27

[74] Chen L,Lu L.MiR-132 inhibits migration and invasion and increases chemosensitivity of cisplatin-resistant oral squamous cell carcinoma cells via targeting TGF-β1.Bioengineered2020;11:91-102 PMCID:PMC6961592

[75] Luo HQ,Ren J.MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.Sci Rep2024;14:6681 PMCID:PMC10954770

[76] Chen S,Wang C.Forkhead box D1 promotes EMT and chemoresistance by upregulating lncRNA CYTOR in oral squamous cell carcinoma.Cancer Lett2021;503:43-53

[77] Yang S,Zhu YH,Wang W.lncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR-124-3p.Head Neck2021;43:2712-23

[78] Yuan F,Zhou Z.[Retracted] Long non-coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis.Int J Mol Med2024;53:31 PMCID:PMC10903928

[79] Yan P,Zhang Z.LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression.Int J Oncol2019;55:988-1002 PMCID:PMC6776185

[80] Hong X,Liang Y.Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1.Mol Cancer2020;19:33 PMCID:PMC7023763

[81] Yuan Z,Liu D.Long noncoding RNA LINC-PINT regulates laryngeal carcinoma cell stemness and chemoresistance through miR-425-5p/PTCH1/SHH axis.J Cell Physiol2019;234:23111-22

[82] Liu J,Tang Q.Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C.J Cancer Res Clin Oncol2021;147:2867-77

[83] Song A,Chu W.Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma.Int J Biol Sci2021;17:430-47 PMCID:PMC7893581

[84] Diener C,Meese E.Emerging concepts of miRNA therapeutics: from cells to clinic.Trends Genet2022;38:613-26

[85] Kara G,Ozpolat B.RNAi-based therapeutics and tumor targeted delivery in cancer.Adv Drug Deliv Rev2022;182:114113

[86] Jiménez-Morales JM,Reyes-Abrahantes A.MicroRNA delivery systems in glioma therapy and perspectives: a systematic review.J Control Release2022;349:712-30

[87] Han J,Jones BT,Gillett F.A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming.Science2020;370:eabc9546 PMCID:PMC8177725

[88] Statello L,Chen LL.Gene regulation by long non-coding RNAs and its biological functions.Nat Rev Mol Cell Biol2021;22:96-118 PMCID:PMC7754182

[89] Nojima T.Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics.Nat Rev Mol Cell Biol2022;23:389-406

[90] Zhang Y,Cui X,Yang Y.Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA.Cell Death Differ2022;29:1850-63 PMCID:PMC9433379

[91] Singh D,Gacche RN.Long non-coding RNA mediated drug resistance in breast cancer.Drug Resist Updat2022;63:100851

[92] Eptaminitaki GC,Bonavida B.Long non-coding RNAs (lncRNAs) signaling in cancer chemoresistance: From prediction to druggability.Drug Resist Updat2022;65:100866

[93] Yu Z,Chen S.Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy.Drug Resist Updat2023;67:100915

[94] Gao Y,Guo S.Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data.Nucleic Acids Res2021;49:D1251-8 PMCID:PMC7779028

[95] Carlevaro-Fita J, Lanzós A, Feuerbach L, et al; PCAWG Drivers and Functional Interpretation Group; PCAWG Consortium. Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.Commun Biol2020;3:56 PMCID:PMC7002399

[96] Ghosh S.Cisplatin: The first metal based anticancer drug.Bioorg Chem2019;88:102925

[97] Dasari S.Cisplatin in cancer therapy: molecular mechanisms of action.Eur J Pharmacol2014;740:364-78 PMCID:PMC4146684

[98] Perego P.Tackling cisplatin resistance in ovarian cancer: what can we do?.Cancer Drug Resist2021;4:755-7 PMCID:PMC8992457

[99] Amable L.Cisplatin resistance and opportunities for precision medicine.Pharmacol Res2016;106:27-36

[100] Galluzzi L,Michels J.Systems biology of cisplatin resistance: past, present and future.Cell Death Dis2014;5:e1257 PMCID:PMC4047912

[101] Xie R,Huang M.NAT10 drives cisplatin chemoresistance by enhancing ac4C-associated DNA repair in bladder cancer.Cancer Res2023;83:1666-83

[102] Shi ZD,Han XX.Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.Mol Cancer2022;21:37 PMCID:PMC8819945

[103] Wu J,Li J.CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis.Drug Resist Updat2023;66:100913

[104] Oh SJ,Son MK.TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway.Nat Commun2023;14:2691 PMCID:PMC10172196

[105] Xiang L,Liu J.MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis.Sci Bull2021;66:1773-88

[106] Tyagi A,Chandrasekaran AP.CRISPR/Cas9-based genome-wide screening for deubiquitinase subfamily identifies USP1 regulating MAST1-driven cisplatin-resistance in cancer cells.Theranostics2022;12:5949-70 PMCID:PMC9373805

[107] Limagne E,Thibaudin M.MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells.Cancer Cell2022;40:136-52.e12

[108] Bray F,Soerjomataram I,Torre LA.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2018;68:394-424

[109] Hong S,Yu G.Gemcitabine plus cisplatin versus fluorouracil plus cisplatin as first-line therapy for recurrent or metastatic nasopharyngeal carcinoma: final overall survival analysis of GEM20110714 phase III study.J Clin Oncol2021;39:3273-82 PMCID:PMC8500603

[110] Tang QN,Qi B.Effect of concurrent chemoradiotherapy with nedaplatin vs cisplatin on the long-term outcomes of survival and toxic effects among patients with stage II to IVB nasopharyngeal carcinoma: a 5-year follow-up secondary analysis of a randomized clinical trial.JAMA Netw Open2021;4:e2138470 PMCID:PMC8689390

[111] Zheng ZQ,Guan JL.Long noncoding RNA TINCR-mediated regulation of acetyl-CoA metabolism promotes nasopharyngeal carcinoma progression and chemoresistance.Cancer Res2020;80:5174-88

[112] Xue F,Xu L.LncRNA NEAT1/miR-129/Bcl-2 signaling axis contributes to HDAC inhibitor tolerance in nasopharyngeal cancer.Aging2020;12:14174-88 PMCID:PMC7425502

[113] Yang J,Wang W,Yu X.Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.Signal Transduct Target Ther2023;8:210 PMCID:PMC10203321

[114] Tang J,Xiao D,Tao Y.The chromatin-associated RNAs in gene regulation and cancer.Mol Cancer2023;22:27 PMCID:PMC9903551

[115] Johnson DE,Leemans CR,Bauman JE.Head and neck squamous cell carcinoma.Nat Rev Dis Primers2020;6:92 PMCID:PMC7944998

[116] Sun S,Guo W.STAT3/HOTAIR signaling axis regulates HNSCC growth in an EZH2-dependent manner.Clin Cancer Res2018;24:2665-77

[117] Jiang Y,Tong T.lncRNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5.Mol Ther2022;30:448-67 PMCID:PMC8753295

[118] Steuer CE,Parks JR,Saba NF.An update on larynx cancer.CA Cancer J Clin2017;67:31-50

[119] Li R,Zhan J.Long noncoding RNA FOXD2-AS1 enhances chemotherapeutic resistance of laryngeal squamous cell carcinoma via STAT3 activation.Cell Death Dis2020;11:41 PMCID:PMC6971019

[120] Pillai J,Dixit R.A systematic review of proteomic biomarkers in oral squamous cell cancer.World J Surg Oncol2021;19:315 PMCID:PMC8555221

[121] Tian T,Pan G.Long noncoding RNA MPRL promotes mitochondrial fission and cisplatin chemosensitivity via disruption of pre-miRNA processing.Clin Cancer Res2019;25:3673-88 PMCID:PMC8725174

[122] Filetti S, Durante C, Hartl D, et al; the ESMO Guidelines Committee. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol2019;30:1856-83

[123] Shi L,Sun Z et al.LncRNA GLTC targets LDHA for succinylation and enzymatic activity to promote progression and radioiodine resistance in papillary thyroid cancer.Cell Death Differ2023;30:1517-32 PMCID:PMC10244348

[124] Wang Y,Wang Z.LncRNA-p23154 promotes the invasion-metastasis potential of oral squamous cell carcinoma by regulating Glut1-mediated glycolysis.Cancer Lett2018;434:172-83

[125] Sang L,Yang Z.Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress.Nat Metab2021;3:90-106

[126] Tan DSW,Leong HS.Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma.Nat Med2017;23:1167-75

[127] Zhang L,Zhu XW.Long non-coding RNAs in Oral squamous cell carcinoma: biologic function, mechanisms and clinical implications.Mol Cancer2019;18:102 PMCID:PMC6535863

[128] Nair L,Basu U.Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery.Nat Rev Mol Cell Biol2020;21:123-36 PMCID:PMC7107043

[129] Zhang L,Su X.Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application.Mol Cancer2020;19:48 PMCID:PMC7050126

[130] Jiang W,Chen X,Zhu X.The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy.Mol Cancer2021;20:116 PMCID:PMC8424797

[131] Zhou WY,Liu J,Ju HQ.Circular RNA: metabolism, functions and interactions with proteins.Mol Cancer2020;19:172 PMCID:PMC7734744

[132] Cheng J,Wang W,Sui G.Circular RNAs with protein-coding ability in oncogenesis.Biochim Biophys Acta Rev Cancer2023;1878:188909

[133] Zhang Q,Zhou Q.Roles of circRNAs in the tumour microenvironment.Mol Cancer2020;19:14 PMCID:PMC6977266

[134] Pisignano G,Visal TH,Ladomery M.Going circular: history, present, and future of circRNAs in cancer.Oncogene2023;42:2783-800 PMCID:PMC10504067

[135] Niu D,Lian J.Circular RNA vaccine in disease prevention and treatment.Signal Transduct Target Ther2023;8:341 PMCID:PMC10493228

[136] Wu S,Zhu H.A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer.Cancer Lett2024;581:216508

[137] Wang Z,Wu P.The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin.Mol Cancer2022;21:29 PMCID:PMC8785480

[138] Hong X,Li J.CircIPO7 promotes nasopharyngeal carcinoma metastasis and cisplatin chemoresistance by facilitating YBX1 nuclear localization.Clin Cancer Res2022;28:4521-35

[139] Li Q,Xu C.Chemotherapy-induced senescence reprogramming promotes nasopharyngeal carcinoma metastasis by circRNA-mediated PKR activation.Adv Sci2023;10:e2205668 PMCID:PMC10015868

[140] Debnath J,Ryan KM.Autophagy and autophagy-related pathways in cancer.Nat Rev Mol Cell Biol2023;24:560-75 PMCID:PMC9980873

[141] Allen EA.Autophagy in animal development.Cell Death Differ2020;27:903-18 PMCID:PMC7206001

[142] Gao W,Niu M.circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway.Mol Cancer2020;19:166 PMCID:PMC7686732

[143] Liu F,Qin L.Circular RNA EIF6 (Hsa_circ_0060060) sponges miR-144-3p to promote the cisplatin-resistance of human thyroid carcinoma cells by autophagy regulation.Aging2018;10:3806-20 PMCID:PMC6326687

[144] Li X,Ma B.Autophagy and autophagy-related proteins in cancer.Mol Cancer2020;19:12 PMCID:PMC6975070

[145] Ji X,Huang J,Sun W.ALKBH5-induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2.Cancer Sci2023;114:2318-34 PMCID:PMC10236620

[146] Cui Y,Liu L.m⁶A-modified circFOXK2 targets GLUT1 to accelerate oral squamous cell carcinoma aerobic glycolysis.Cancer Gene Ther2023;30:163-71

[147] Zhao W,Wu J.High-throughput microarray reveals the epitranscriptome-wide landscape of m⁶A-modified circRNA in oral squamous cell carcinoma.BMC Genomics2022;23:611 PMCID:PMC9400228

[148] Li J,Yang J.IGF2BP2-m6A-circMMP9 axis recruits ETS1 to promote TRIM59 transcription in laryngeal squamous cell carcinoma.Sci Rep2024;14:3014 PMCID:PMC10847447

[149] Wu P,Liu Y.N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway.Cell Death Dis2021;12:298 PMCID:PMC7979824

[150] Jiang X,Conrad M.Ferroptosis: mechanisms, biology and role in disease.Nat Rev Mol Cell Biol2021;22:266-82 PMCID:PMC8142022

[151] Sun S,Jiang J,Min J.Targeting ferroptosis opens new avenues for the development of novel therapeutics.Signal Transduct Target Ther2023;8:372 PMCID:PMC10514338

[152] Zhu J,Su Y.Multifunctional nanolocks with GSH as the key for synergistic ferroptosis and anti-chemotherapeutic resistance.Biomaterials2022;288:121704

[153] Zhang J,Chakraborty P.Microsomal glutathione transferase 1 controls metastasis and therapeutic response in melanoma.Pharmacol Res2023;196:106899 PMCID:PMC10623471

[154] Yuan L,Chen Q.EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.Cell Death Differ2022;29:1513-27 PMCID:PMC9346003

[155] Roh JL,Jang H.Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis.Redox Biol2017;11:254-62 PMCID:PMC5198738

[156] Shin D,Lee J.Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer.Free Radic Biol Med2018;129:454-62

[157] Lee J,Shin D.Inhibition of glutaredoxin 5 predisposes cisplatin-resistant head and neck cancer cells to ferroptosis.Theranostics2020;10:7775-86 PMCID:PMC7359084

[158] Yang JY,He KY.HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.Cell Death Dis2024;15:158 PMCID:PMC10881472

[159] Angeli JP, Krysko DV, Conrad M. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion.Nat Rev Cancer2019;19:405-14

[160] Li B,Peng X.Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers.Biomed Pharmacother2020;130:110710

[161] Sun X,Chen R.Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis.Hepatology2016;64:488-500 PMCID:PMC4956496

[162] Jiang Z,Yan M.TYRO3 induces anti-PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis.J Clin Invest2021;131:139434 PMCID:PMC8262501

[163] Qi R,Li K.Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs.Drug Resist Updat2023;68:100960

[164] Liang J,Huang Y.MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma.Drug Resist Updat2024;73:101057

[165] Zhang X,Ma L.Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma.Cancer Commun2022;42:287-313 PMCID:PMC9017758

[166] Jiang M,Liu K.Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1.Mol Cancer2023;22:113 PMCID:PMC10351131

[167] Xi Y,Wu D.CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p.Mol Cancer2022;21:145 PMCID:PMC9284725

[168] Zhang C,Jin S,Guo R.Ferroptosis in cancer therapy: a novel approach to reversing drug resistance.Mol Cancer2022;21:47 PMCID:PMC8840702

[169] Zhang C,Gao X.Platinum-based drugs for cancer therapy and anti-tumor strategies.Theranostics2022;12:2115-32 PMCID:PMC8899578

[170] Huang Y,Su Y.Combination therapy based on dual-target biomimetic nano-delivery system for overcoming cisplatin resistance in hepatocellular carcinoma.J Nanobiotechnology2023;21:89 PMCID:PMC10015699

[171] Siemer S,Scholz P.Targeting cancer chemotherapy resistance by precision medicine-driven nanoparticle-formulated cisplatin.ACS Nano2021;15:18541-56

[172] Zhang R,Luo M.Poly(β-cyclodextrin)/platinum prodrug supramolecular nano system for enhanced cancer therapy: synthesis and in vivo study.Carbohydr Polym2022;292:119695

[173] Chen J,Yuan Y.Exploiting the acquired vulnerability of cisplatin-resistant tumors with a hypoxia-amplifying DNA repair-inhibiting (HYDRI) nanomedicine.Sci Adv2021;7:eabc5267 PMCID:PMC7997498

[174] Chen Y,Zhou W.Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia.J Nanobiotechnology2021;19:246 PMCID:PMC8365946

[175] Pan WL,Meng W.Microenvironment-driven sequential ferroptosis, photodynamic therapy, and chemotherapy for targeted breast cancer therapy by a cancer-cell-membrane-coated nanoscale metal-organic framework.Biomaterials2022;283:121449

[176] Zhang Z,Hu N.Ferroptosis-induced anticancer effect of resveratrol with a biomimetic nano-delivery system in colorectal cancer treatment.Asian J Pharm Sci2022;17:751-66 PMCID:PMC9640689

[177] Li K,Li M.Multienzyme-like reactivity cooperatively impairs glutathione peroxidase 4 and ferroptosis suppressor protein 1 pathways in triple-negative breast cancer for sensitized ferroptosis therapy.ACS Nano2022;16:2381-98

[178] Li K,He Y.Oxygen self-generating nanoreactor mediated ferroptosis activation and immunotherapy in triple-negative breast cancer.ACS Nano2023;17:4667-87

[179] Chen D,Qu X.Metal-free polymer nano-photosensitizer actuates ferroptosis in starved cancer.Biomaterials2023;292:121944

[180] Liu J,Li S.The biology, function, and applications of exosomes in cancer.Acta Pharm Sin B2021;11:2783-97 PMCID:PMC8463268

[181] Wu J,Zhang P.Tumor-derived exosomes: immune properties and clinical application in lung cancer.Cancer Drug Resist2022;5:102-13 PMCID:PMC8992595

[182] Wang Z,Bach DH.Induction of m⁶A methylation in adipocyte exosomal LncRNAs mediates myeloma drug resistance.J Exp Clin Cancer Res2022;41:4 PMCID:PMC8722039

[183] Shi L,Huang Y.Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small cell lung cancer.Clin Transl Med2022;12:e989 PMCID:PMC9299573

[184] Pan Z,Zhang J.A novel protein encoded by exosomal circATG4B induces oxaliplatin resistance in colorectal cancer by promoting autophagy.Adv Sci2022;9:e2204513 PMCID:PMC9762280

[185] Jing X,Ding K.Exosome-transmitted miR-769-5p confers cisplatin resistance and progression in gastric cancer by targeting CASP9 and promoting the ubiquitination degradation of p53.Clin Transl Med2022;12:e780 PMCID:PMC9076018

[186] Liu X,Gao G.Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling.J Nanobiotechnology2023;21:45 PMCID:PMC9906870

[187] Deng J,Lv C.Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.Theranostics2023;13:5057-74 PMCID:PMC10526671

[188] Zhang F,Qian H,Xu W.Exosomal circRNA: emerging insights into cancer progression and clinical application potential.J Hematol Oncol2023;16:67 PMCID:PMC10294326

[189] Guo X,Yang DH.Exosomal circular RNAs: a chief culprit in cancer chemotherapy resistance.Drug Resist Updat2023;67:100937

[190] Li K.PROTACs: past, present and future.Chem Soc Rev2022;51:5214-36 PMCID:PMC10237031

[191] Marei H,Kee YS.Antibody targeting of E3 ubiquitin ligases for receptor degradation.Nature2022;610:182-9 PMCID:PMC9534761

[192] Xiong Y,Yim H.Bridged proteolysis targeting chimera (PROTAC) enables degradation of undruggable targets.J Am Chem Soc2022;144:22622-32 PMCID:PMC9772293

[193] Ghidini A,Halloy F,Hall J.RNA-PROTACs: degraders of RNA-binding proteins.Angew Chem Int Ed Engl2021;60:3163-9 PMCID:PMC7898822

[194] Li X,Zheng Q,Chen S.Proteolysis-targeting chimeras (PROTACs) in cancer therapy.Mol Cancer2022;21:99 PMCID:PMC8996410

[195] Wu Y,Yang G.A physiologically responsive nanocomposite hydrogel for treatment of head and neck squamous cell carcinoma via proteolysis-targeting chimeras enhanced immunotherapy.Adv Mater2023;35:e2210787

[196] Jin J,Zhao Z.Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer.JCI Insight2022;7:e160606 PMCID:PMC9746828

[197] Kuismi CC.Lighting the way to tumor destruction.Trends Pharmacol Sci2023;44:750-2 PMCID:PMC10691509

[198] Yang F,Wang Y.Targeted biomolecule regulation platform: a split-and-mix PROTAC approach.J Am Chem Soc2023;145:7879-87

[199] Collins R.What makes UK Biobank special?.Lancet2012;379:1173-4

[200] Zhang C,Tang R.Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment.J Hematol Oncol2023;16:114 PMCID:PMC10680201

[201] Tayebi Arasteh S,Lotfinia M.Large language models streamline automated machine learning for clinical studies.Nat Commun2024;15:1603 PMCID:PMC10881983