Hsa-circ-0006091 Modulates the Proliferation of Hepatocellular Carcinoma Via the MiR-622/CCNB1 Axis

Overview

Journal Turk J Med Sci

Specialty General Medicine

Date 2024 May 30

PMID 38813026

Authors

Xiaofeng Zhao

Ling He

Affiliations

Soon will be listed here.

Abstract

Background/aim: Hepatocellular carcinoma (HCC) is a common type of cancer. We hypothesize that circular RNA-0006091 (circ-0006091) affects the progression of HCC. The study aims to investigate the effect of circ-0006091 in HCC cells.

Materials And Methods: The levels of circ-0006091, microRNA-622 (miR-622), and cyclin B1 (CCNB1) were assayed using qRT-PCR and western blotting. The metastasis of the HCC cells was measured with wound healing and transwell assays. The protein expression levels of MMP-2 and MMP-9 were assayed with western blotting. Dual-luciferase reporter and RNA-pulldown assays were used to determine the link between miR-622 and circ-0006091 or CCNB1. Mice-based tests were used to determine the effect of circ-0006091 on the proliferation of HCC cells.

Results: The levels of circ-0006091 and CCNB1 were increased in the HCC cells, but miR-622 was down-regulated. Deficiency of circ-0006091 reduced the metastasis of the HCC cells, and silencing of circ-0006091 decreased the activities of MMP-2 and MMP-9 in the same cells. Circ-0006091 modulated the CCNB1 level in the HCC cells via miR-622. Silencing of circ-0006091 suppressed the proliferation of the HCC cells in vivo.

Conclusion: Circ-0006091 regulated HCC cell metastasis via the miR-622/CCNB1 axis, a possible therapeutic target in managing HCC.

References

Liu H, Liu Y, Liu W, Zhang W, Xu J . EZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma. Nat Commun. 2015; 6:8494. PMC: 4598861. DOI: 10.1038/ncomms9494. View

Ni C, Yang S, Ji Y, Duan Y, Yang W, Yang X . Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma. Cell Death Discov. 2021; 7(1):270. PMC: 8486831. DOI: 10.1038/s41420-021-00664-0. View

Xia P, Zhang H, Xu K, Jiang X, Gao M, Wang G . MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma. Cell Death Dis. 2021; 12(7):691. PMC: 8270967. DOI: 10.1038/s41419-021-03973-5. View

Yao Z, Luo J, Hu K, Lin J, Huang H, Wang Q . ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol. 2017; 11(4):422-437. PMC: 5527481. DOI: 10.1002/1878-0261.12045. View

Zhou Z, Li Y, Hao H, Wang Y, Zhou Z, Wang Z . Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis. Cell Transplant. 2019; 28(1_suppl):76S-86S. PMC: 7016461. DOI: 10.1177/0963689719893950. View

Wei Y, Chen X, Liang C, Ling Y, Yang X, Ye X . A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma. Hepatology. 2019; 71(1):130-147. DOI: 10.1002/hep.30795. View

Kim D, Talati C, Kim R . Hepatocellular carcinoma (HCC): beyond sorafenib-chemotherapy. J Gastrointest Oncol. 2017; 8(2):256-265. PMC: 5401857. DOI: 10.21037/jgo.2016.09.07. View

Yang J, Lu J, Yin N, Sun J, Pu J, Zang J . miR-622 Counteracts the NUAK1-Induced Gastric Cancer Cell Proliferation and the Antioxidative Stress. Dis Markers. 2022; 2022:9616764. PMC: 9303142. DOI: 10.1155/2022/9616764. View

Heimbach J, Kulik L, Finn R, Sirlin C, Abecassis M, Roberts L . AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2017; 67(1):358-380. DOI: 10.1002/hep.29086. View

10.

Si T, Huang Z, Jiang Y, Walker-Jacobs A, Gill S, Hegarty R . Expression Levels of Three Key Genes CCNB1, CDC20, and CENPF in HCC Are Associated With Antitumor Immunity. Front Oncol. 2021; 11:738841. PMC: 8515852. DOI: 10.3389/fonc.2021.738841. View

11.

Zhang H, Zhang X, Li X, Meng W, Bai Z, Rui S . Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer. J Cell Physiol. 2018; 234(1):619-631. DOI: 10.1002/jcp.26816. View

12.

Song W, Feng X, Gong S, Chen J, Wang S, Xing D . microRNA-622 acts as a tumor suppressor in hepatocellular carcinoma. Cancer Biol Ther. 2015; 16(12):1754-63. PMC: 4847826. DOI: 10.1080/15384047.2015.1095402. View

13.

Lv L, Wang X . MicroRNA-296 Targets Specificity Protein 1 to Suppress Cell Proliferation and Invasion in Cervical Cancer [ 26(5) (2018) 775-783]. Oncol Res. 2021; 28(7):835. PMC: 8420896. DOI: 10.3727/096504021X16261699250204. View

14.

Colecchia A, Schiumerini R, Cucchetti A, Cescon M, Taddia M, Marasco G . Prognostic factors for hepatocellular carcinoma recurrence. World J Gastroenterol. 2014; 20(20):5935-50. PMC: 4033434. DOI: 10.3748/wjg.v20.i20.5935. View

15.

Liang H, Zhang X, Liu B, Jia G, Li W . Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271. Am J Cancer Res. 2017; 7(7):1566-1576. PMC: 5523036. View

16.

Huang G, Liang M, Liu H, Huang J, Li P, Wang C . 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. PMC: 7734058. DOI: 10.1038/s41419-020-03276-1. View

17.

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. PMC: 8973770. DOI: 10.1080/21655979.2021.2006952. View

18.

Targhazeh N, Yousefi B, Asghari S, Mohammadnejhad R, Mansouri P, Valizadeh A . MiR-622 acts as a tumor suppressor to induce cell apoptosis and inhibit metastasis in human prostate cancer. Andrologia. 2021; 53(9):e14174. DOI: 10.1111/and.14174. View

19.

Catalanotto C, Cogoni C, Zardo G . MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016; 17(10). PMC: 5085744. DOI: 10.3390/ijms17101712. View

20.

Diaz-Gonzalez A, Reig M, Bruix J . Treatment of Hepatocellular Carcinoma. Dig Dis. 2016; 34(5):597-602. DOI: 10.1159/000445275. View