Hsa_Circ_0104206 is An Oncogenic circRNA in Colon Cancer by Targeting Mir-188–3p/CCNA2 Axis

Abstract

The identification of specific biomarkers is essential to improve cancer therapy, and circular RNAs (circRNAs) have great potency to be biomarkers. We harbor the goal to unveil the role of circ_0104206 in colon cancer (CC). The relative expressions of circ_0104206, miR-188–3p and CCNA2 in different groups were studied using real-time quantitative PCR (qPCR) or western blotting. The proliferative and migratory capacity of cancer cells were monitored via CCK-8, colony formation and Transwell assays. The transplanted tumor models were generated to analyze circ_0104206’s role in vivo. The putative relationship between miR-188–3p and circ_0104206 or CCNA2 by bioinformatics tools was testified through dual-luciferase or RIP assay. The abnormal elevation of circ_0104206 expression was observed in CC. Circ_0104206 silencing repressed CC cell proliferative and migratory behaviors, and also decelerated tumor development in animal models. MiR-188–3p was directly targeted by circ_0104206, and its inhibitor had the ability to reverse the anticancer effects of circ_0104206 silencing on CC cells. CCNA2 was a target downstream of circ_0104206/miR-188–3p network. Moreover, the repressive effects of CCNA2 absence on cell proliferation and migration were attenuated by miR-188–3p inhibitor. In conclusion, Circ_0104206 plays oncogenic roles in CC via the implication of miR-188–3p/CCNA2 network, which further discloses CC pathogenesis and supplies potential markers for CC.

Key words

circ_0104206 - miR-188–3p - CCNA2 - colon cancer

Publication History

Received: 24 October 2022

Accepted after revision: 02 March 2023

Article published online:
05 June 2023

• References

• 1 Birkett RT, Chamely E, Concors SJ. et al. Overuse and limited benefit of chemotherapy for stage II colon cancer in young patients. Clin Colorectal Cancer 2019; 18: 292-300
• 2 Altieri MS, Thompson H, Pryor A. et al. Incidence of colon resections is increasing in the younger populations: should an early initiation of colon cancer screening be implemented?. Surg Endosc 2021; 35: 3636-3641
• 3 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-249
• 4 Snaebjornsson P, Jonasson L, Olafsdottir EJ. et al. Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years. Int J Cancer 2017; 141: 531-539
• 5 Wang W, Xiao J, Shen S. et al. Emerging effect of anesthesia on post-operative tumor recurrence and metastasis. J Int Med Res 2019; 47: 3550-3558
• 6 Latowska J, Grabowska A, Zarębska Ż. et al. Non-coding RNAs in brain tumors, the contribution of lncRNAs, circRNAs, and snoRNAs to cancer development - their diagnostic and therapeutic potential. Int J Mol Sci 2020; 21 7001
• 7 Tachiwana H, Saitoh N. Nuclear long non-coding RNAs as epigenetic regulators in cancer. Curr Med Chem 2021; 28: 5098-5109
• 8 Lyu M, Li X, Shen Y. et al. CircATRNL1 and circZNF608 inhibit ovarian cancer by sequestering miR-152-5p and encoding protein. Front Genet 2022; 13: 784089
• 9 Chen Z, Qi Z, He D. et al. Strategy for scanning peptide-coding circular RNAs in colorectal cancer based on bioinformatics analysis and experimental assays. Front Cell Dev Biol 2021; 9: 815895
• 10 Zhang S, Sun J, Gu M. et al. Circular RNA: a promising new star for the diagnosis and treatment of colorectal cancer. Cancer Med 2021; 10: 8725-8740
• 11 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: 13
• 12 Zhang Y, Zhang Y, Feng Y. et al. Construction of circRNA-based ceRNA network and its prognosis-associated subnet of clear cell renal cell carcinoma. Cancer Med 2021; 10: 8210-8221
• 13 Meng L, Jiang YP, Zhu J. et al. MiR-188-3p/GPR26 modulation functions as a potential regulator in manipulating glioma cell properties. Neurol Res 2020; 42: 222-227
• 14 Yao J, Xu G, Zhu L. et al. circGFRA1 Enhances NSCLC progression by sponging miR-188-3p. Onco Targets Ther 2020; 13: 549-558
• 15 Pei J, Zhang J, Yang X. et al. TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p. Cancer Cell Int 2019; 19: 75
• 16 Zhang J, Liu H, Zhao P. et al. Has_circ_0055625 from circRNA profile increases colon cancer cell growth by sponging miR-106b-5p. J Cell Biochem 2019; 120: 3027-3037
• 17 Yang S, Gao S, Liu T. et al. Circular RNA SMARCA5 functions as an anti-tumor candidate in colon cancer by sponging microRNA-552. Cell Cycle 2021; 20: 689-701
• 18 Wang Y, Wang L, Wang W. et al. Overexpression of circular RNA hsa_circ_0001038 promotes cervical cancer cell progression by acting as a ceRNA for miR-337-3p to regulate cyclin-M3 and metastasis-associated in colon cancer 1 expression. Gene 2020; 733: 144273
• 19 He J, Zhao H, Liu X. et al. Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosome‑mediated circ‑HMGCS1 via the miR‑34a‑5p/SGPP1 axis. Oncol Rep 2020; 44: 2429-2442
• 20 Wang L, Peng X, Lu X. et al. Inhibition of hsa_circ_0001313 (circCCDC66) induction enhances the radio-sensitivity of colon cancer cells via tumor suppressor miR-338-3p: Effects of cicr_0001313 on colon cancer radio-sensitivity. Pathol Res Pract 2019; 215: 689-696
• 21 Gan Y, Li Y, Li T. et al. CCNA2 acts as a novel biomarker in regulating the growth and apoptosis of colorectal cancer. Cancer Manag Res 2018; 10: 5113-5124
• 22 Dong S, Huang F, Zhang H. et al. Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma. Biosci Rep 2019; 39 BSR20182306
• 23 Guo F, Zhang K, Li M. et al. miR‑508–3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7. Int J Oncol 2020; 57: 264-276