Construction of circular RNA-based competing endogenous RNA network in colon cancer

Abstract

Circular RNAs (CircRNAs) are now under discussion as novel promising biomarkers for patients with various tumors. Our study aimed to identify circRNAs related to the progression of colon cancer and to further investigate their roles in the development of colon cancer base on The Cancer Genome Atlas database. The competing endogenous RNA (ceRNA) network was constructed based on 4 circRNAs, 14 miRNAs, and 229 mRNAs. Meanwhile, three hub genes were identified via the protein protein interaction networks (PPI) network. It should be noted that only RUNX1 targeted by circ-0084615 and mir-330-3p was confirmed as a survival-related gene. Further analyses indicated the possible function of RUNX1 in colon progression, such as angiogenesis, epithelial–mesenchymal transition, hedgehog signaling and so on. Further investigations were conducted into the correlation between RUNX1 expression profiles and immune cells. Finally, we validated the expression of the circ-0084615/mir-330-3p/RUNX1 axis in clinical specimens. In conclusion, we constructed ceRNA network and revealed that the circ-0084615/mir-330-3p/RUNX1 axis serves as a critical role in colon cancer.

Keywords

ceRNA / circRNAs / colon cancer / RUNX1 / tumor progression

References

[1] Nogueira L, May F, Yabroff K, Siegel R. Racial disparities in receipt of guideline-concordant care for early-onset colorectal cancer in the United States. J Clin Oncol. Published online November 8; 2023;JCO2300539.

[2] Zwanenburg E, El Klaver C, Wisselink D, et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): 5-year results of a randomized multicenter trial. J Clin Oncol. 2024;42(2):140-145.

[3] Montroni I, Ugolini G, Saur N, et al. Predicting functional recovery and quality of life in older patients undergoing colorectal cancer surgery: real-world data from the international GOSAFE study. J Clin Oncol. 2023;41(34):5247-5262.

[4] Brody H. Colorectal cancer. Nature. 2015;521(7551):S1.

[5] Arun G, Diermeier S, Akerman M, et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev. 2016;30(1):34-51.

[6] Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071-1076.

[7] Salzman J. Circular RNA expression: its potential regulation and function. Trends Genet. 2016;32(5):309-316.

[8] Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 is a circular RNA that can Be translated and functions in myogenesis. Mol Cell. 2017;66(1):22-37.e9.

[9] Pamudurti NR, Bartok O, Jens M, et al. Translation of CircRNAs. Mol Cell. 2017;66(1):9-21.e7.

[10] Guo JU, Agarwal V, Guo H, Bartel DP. Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 2014;15(7):409.

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

[12] Guarnerio J, Bezzi M, Jeong JC, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 2016;166(4):1055-1056.

[13] Holdt LM, Stahringer A, Sass K, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun. 2016;7:12429.

[14] 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.

[15] Lu J, Zhang PY, Xie JW, et al. Hsa_circ_0000467 promotes cancer progression and serves as a diagnostic and prognostic biomarker for gastric cancer. J Clin Lab Anal. 2019;33(3):e22726.

[16] Liu Z, Zheng N, Li J, et al. N6-methyladenosine-modified circular RNA QSOX1 promotes colorectal cancer resistance to anti-CTLA-4 therapy through induction of intratumoral regulatory T cells. Drug Resist Updat. 2022;65:100886.

[17] Yang Z, Wang W, Zhao L, et al. Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs. Sci Adv. 2021;7(9):eabb0737.

[18] Lozano E, Macias R, Monte M, et al. Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy. Hepatology. 2019;70(4):1246-1261.

[19] Mansoori B, Mohammadi A, Naghizadeh S, et al. miR-330 suppresses EMT and induces apoptosis by downregulating HMGA2 in human colorectal cancer. J Cell Physiol. 2020;235(2):920-931.

[20] Xin Y, He X, Zhao W, et al. LncRNA PCAT6 increased cholangiocarcinoma cell proliferation and invasion via modulating miR-330-5p. Am J Trans Res. 2019;11(9):6185-6195.

[21] Huang Y, Sun H, Ma X, et al. HLA-F-AS1/miR-330-3p/PFN1 axis promotes colorectal cancer progression. Life Sci. 2019;117180:117180.

[22] Wang Y, Xu R, Zhang D, et al. Circ-ZKSCAN1 regulates FAM83A expression and inactivates MAPK signaling by targeting miR-330-5p to promote non-small cell lung cancer progression. Transl Lung Cancer Res. 2019;8(6):862-875.

[23] Li J, Yin Y, Huang H, et al. RUNX1 methylation as a cancer biomarker in differentiating papillary thyroid cancer from benign thyroid nodules. Epigenomics. 2023;15(23):1257-1272.

[24] Yu X, Zhao P, Luo Q, et al. RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression. Oncogene. 2023;43:420-433.

[25] Li Q, Lai Q, He C, et al. RUNX1 promotes tumour metastasis by activating the Wnt/beta-catenin signalling pathway and EMT in colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):334.

[26] Sun L, Wang L, Chen T, et al. LncRNA RUNX1-IT1 which is downregulated by hypoxia-driven histone deacetylase 3 represses proliferation and cancer stem-like properties in hepatocellular carcinoma cells. Cell Death Dis. 2020;11(2):95.

[27] Fang J, Hong H, Xue X, et al. A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548g in the cytoplasm and interacting with YBX1 in the nucleus. Cancer Lett. 2019;442:222-232.

RIGHTS & PERMISSIONS

2024 The Authors. Precision Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital.