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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Hsa_circ_0008092 Contributes to Cell Proliferation and Metastasis in Hepatocellular Carcinoma via the miR-502-5p/CCND1 Axis

Author(s): Yilihamu Maimaiti, Aihesan Kamali, Peng Yang, Kai Zhong and Xiaokaiti Abuduhadeer*

Volume 29, Issue 7, 2022

Published on: 22 August, 2022

Page: [595 - 604] Pages: 10

DOI: 10.2174/0929866529666220721090209

Price: $65

Abstract

Background: The present study was targeted at investigating the effects of hsa_circRNA_0008092 (circ_0008092) on hepatocellular carcinoma (HCC) cell proliferation, migration, invasion and apoptosis, and its related mechanism.

Methods: The gene expression profiles of GSE166678 were downloaded from the Gene Expression Omnibus database, and differentially expressed circRNAs in human HCC were screened out. Besides, circ_0008092, microRNA-502-5p (miR-502-5p) and cyclin D1 (CCND1) expressions in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRTPCR). Cell countering kit-8 (CCK-8), Transwell and flow cytometry assays were used to detect the proliferation, migration, invasion and apoptosis of HCC cells. Bioinformatics was utilized to predict the targeted relationships between miR-502-5p and circ_0008092, as well as miR-502-5p and CCND1 mRNA 3'-untranslated region (3’UTR). Western blot assay was applied to detect CCND1 protein expression in HCC cells.

Results: Circ_0008092 was highly expressed in HCC tissues and cells, which was associated with a shorter survival time in patients with HCC. Circ_0008092 overexpression promoted proliferation, migration and invasion, and inhibited apoptosis of HCC cells; circ_0008092 knockdown worked oppositely. Circ_0008092 directly targeted miR-502-5p and negatively modulated miR-502-5p expression. CCND1 was a target gene of miR-502-5p, and was positively and indirectly modulated by circ_0008092.

Conclusion: Our data suggest that circ_0008092 promotes HCC progression by regulating the miR- 502-5p/CCND1 axis.

Keywords: Hepatocellular carcinoma, circ_0008092, miR-502-5p, CCND1, proliferation, circular RNAs.

Graphical Abstract
[1]
Forner, A.; Reig, M.; Bruix, J. Hepatocellular carcinoma. Lancet, 2018, 391(10127), 1301-1314.
[http://dx.doi.org/10.1016/S0140-6736(18)30010-2] [PMID: 29307467]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Liu, W.; Wang, S.; Yang, Q.; Feng, X.; Yu, B.; Yu, X. 20(s)-ginsenoside Rh2 promotes TRAIL-induced apoptosis by upregulating DR5 in human hepatocellular carcinoma cells. Med. Oncol., 2022, 39(5), 70.
[http://dx.doi.org/10.1007/s12032-022-01663-6] [PMID: 35568793]
[4]
Qu, L.S.; Jin, F.; Guo, Y.M.; Liu, T.T.; Xue, R.Y.; Huang, X.W.; Xu, M.; Chen, T.Y.; Ni, Z.P.; Shen, X.Z. Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. Oncol. Lett., 2016, 11(1), 624-632.
[http://dx.doi.org/10.3892/ol.2015.3958] [PMID: 26870257]
[5]
Ogunwobi, O.O.; Harricharran, T.; Huaman, J.; Galuza, A.; Odumuwagun, O.; Tan, Y.; Ma, G.X.; Nguyen, M.T. Mechanisms of hepatocellular carcinoma progression. World J. Gastroenterol., 2019, 25(19), 2279-2293.
[http://dx.doi.org/10.3748/wjg.v25.i19.2279] [PMID: 31148900]
[6]
Das, A.; Rout, P.K.; Gorospe, M.; Panda, A.C. Rolling circle cDNA synthesis uncovers circular RNA splice variants. Int. J. Mol. Sci., 2019, 20(16), 3988.
[http://dx.doi.org/10.3390/ijms20163988] [PMID: 31426285]
[7]
Cardenas, J.; Balaji, U.; Gu, J. Cerina: Systematic circRNA functional annotation based on integrative analysis of ceRNA interactions. Sci. Rep., 2020, 10(1), 22165.
[http://dx.doi.org/10.1038/s41598-020-78469-x] [PMID: 33335165]
[8]
Wang, M.; Yang, Y.; Yang, J.; Yang, J.; Han, S. circ_KIAA1429 accelerates hepatocellular carcinoma advancement through the mechanism of m6A-YTHDF3-Zeb1. Life Sci., 2020, 257(15), 118082.
[http://dx.doi.org/10.1016/j.lfs.2020.118082] [PMID: 32653519]
[9]
Yu, J.; Xu, Q.G.; Wang, Z.G.; Yang, Y.; Zhang, L.; Ma, J.Z.; Sun, S.H.; Yang, F.; Zhou, W.P. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J. Hepatol., 2018, 68(6), 1214-1227.
[http://dx.doi.org/10.1016/j.jhep.2018.01.012] [PMID: 29378234]
[10]
Bi, J.; Liu, H.; Cai, Z.; Dong, W.; Jiang, N.; Yang, M.; Huang, J.; Lin, T. Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis. Aging, 2018, 10(8), 1964-1976.
[http://dx.doi.org/10.18632/aging.101520] [PMID: 30103209]
[11]
Wang, B.; Duan, R.; Li, Z.B.; Wang, L. Circ-RPL15/miR-146b-3p/VEGFA feedback loop is responsible for triggering proliferation and migration in glioma. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(11), 6204-6210.
[http://dx.doi.org/10.26355/eurrev_202006_21516] [PMID: 32572886]
[12]
Yao, Z.; Xu, R.; Yuan, L.; Xu, M.; Zhuang, H.; Li, Y.; Zhang, Y.; Lin, N. Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11. Cell Death Dis., 2019, 10(12), 945.
[http://dx.doi.org/10.1038/s41419-019-2176-y] [PMID: 31822654]
[13]
Wei, X.; Zheng, W.; Tian, P.; He, Y.; Liu, H.; Peng, M.; Li, X.; Liu, X. Oncogenic hsa_circ_0091581 promotes the malignancy of HCC cell through blocking miR-526b from degrading c-MYC mRNA. Cell Cycle, 2020, 19(7), 817-824.
[http://dx.doi.org/10.1080/15384101.2020.1731945] [PMID: 32116112]
[14]
Chen, L.; Heikkinen, L.; Wang, C.; Yang, Y.; Sun, H.; Wong, G. Trends in the development of miRNA bioinformatics tools. Brief. Bioinform., 2019, 20(5), 1836-1852.
[http://dx.doi.org/10.1093/bib/bby054] [PMID: 29982332]
[15]
Wang, W.; Jo, H.; Park, S.; Kim, H.; Kim, S.I.; Han, Y.; Lee, J.; Seol, A.; Kim, J.; Lee, M.; Lee, C.; Dhanasekaran, D.N.; Ahn, T.; Song, Y.S. Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer. Cancer Lett., 2022, 12, 215735.
[http://dx.doi.org/10.1016/j.canlet.2022.215735] [PMID: 35569696]
[16]
Huang, W.; Huang, F.; Lei, Z.; Luo, H. LncRNA SNHG11 promotes proliferation, migration, apoptosis, and autophagy by regulating hsa-miR-184/AGO2 in HCC. OncoTargets Ther., 2020, 13(14), 413-421.
[http://dx.doi.org/10.2147/OTT.S237161] [PMID: 32021286]
[17]
Li, H.; Liang, J.; Huang, K. The emerging roles of heterogeneous nuclear ribonucleoprotein C in cancer and other diseases. J. Cancer Dis., 2022, 1(1), 1-12.
[18]
Xue, H.; Tian, G.Y. miR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23. Arch. Biochem. Biophys., 2018, 637, 48-55.
[http://dx.doi.org/10.1016/j.abb.2017.11.011] [PMID: 29191386]
[19]
Zhao, Z.; Song, J.; Tang, B.; Fang, S.; Zhang, D.; Zheng, L.; Wu, F.; Gao, Y.; Chen, C.; Hu, X.; Weng, Q.; Yang, Y.; Tu, J.; Ji, J. CircSOD2 induced epigenetic alteration drives hepatocellular carcinoma progression through activating JAK2/STAT3 signaling pathway. J. Exp. Clin. Cancer Res., 2020, 39(1), 259.
[http://dx.doi.org/10.1186/s13046-020-01769-7] [PMID: 33234142]
[20]
Verduci, L.; Strano, S.; Yarden, Y.; Blandino, G. The circRNA-microRNA code: Emerging implications for cancer diagnosis and treatment. Mol. Oncol., 2019, 13(4), 669-680.
[http://dx.doi.org/10.1002/1878-0261.12468] [PMID: 30719845]
[21]
Lu, S.; Zhu, N.; Guo, W.; Wang, X.; Li, K.; Yan, J.; Jiang, C.; Han, S.; Xiang, H.; Wu, X.; Liu, Y.; Xiong, H.; Chen, L.; Gong, Z.; Luo, F.; Hou, W. RNA-seq revealed a circular RNA-microRNA-mRNA regulatory network in hantaan virus infection. Front. Cell. Infect. Microbiol., 2020, 10, 97.
[http://dx.doi.org/10.3389/fcimb.2020.00097] [PMID: 32232013]
[22]
Salamo, O.; Mortaz, E.; Mirsaeidi, M. Noncoding RNAs: New players in pulmonary medicine and sarcoidosis. Am. J. Respir. Cell Mol. Biol., 2018, 58(2), 147-156.
[http://dx.doi.org/10.1165/rcmb.2017-0196TR] [PMID: 28850258]
[23]
Chen, R.X.; Liu, H.L.; Yang, L.L.; Kang, F.H.; Xin, L.P.; Huang, L.R.; Guo, Q.F.; Wang, Y.L. Circular RNA circRNA_0000285 promotes cervical cancer development by regulating FUS. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(20), 8771-8778.
[PMID: 31696463]
[24]
Zhou, G.R.; Huang, D.P.; Sun, Z.F.; Zhang, X.F. Characteristics and prognostic significance of circRNA-100876 in patients with colorectal cancer. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(22), 11587-11593.
[http://dx.doi.org/10.26355/eurrev_201910_19271] [PMID: 33275225]
[25]
Zhou, X.Y.; Yang, H.; Bai, Y.Q.; Li, X.L.; Han, S.Y.; Zhou, B.X. hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis. Cell. Mol. Biol. Lett., 2020, 25(1), 47.
[http://dx.doi.org/10.1186/s11658-020-00238-5] [PMID: 33292166]
[26]
Wang, X.; Wang, X.; Li, W.; Zhang, Q.; Chen, J.; Chen, T. Up-regulation of hsa_circ_0000517 predicts adverse prognosis of hepatocellular carcinoma. Front. Oncol., 2019, 9, 1105.
[http://dx.doi.org/10.3389/fonc.2019.01105] [PMID: 31750237]
[27]
Su, Y.; Lv, X.; Yin, W.; Zhou, L.; Hu, Y.; Zhou, A.; Qi, F. CircRNA CDR1AS functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression. Aging, 2019, 11(19), 8183-8203.
[http://dx.doi.org/10.18632/aging.102312] [PMID: 31581132]
[28]
Long, J.; Bai, Y.; Yang, X.; Lin, J.; Yang, X.; Wang, D.; He, L.; Zheng, Y.; Zhao, H. Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for hepatocellular carcinoma. Cancer Cell Int., 2019, 19(1), 90.
[http://dx.doi.org/10.1186/s12935-019-0817-y] [PMID: 31007608]
[29]
Yu, J.; Yang, M.; Zhou, B.; Luo, J.; Zhang, Z.; Zhang, W.; Yan, Z. CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway. Clin. Sci., 2019, 133(13), 1487-1503.
[http://dx.doi.org/10.1042/CS20190394] [PMID: 31278132]
[30]
You, W.; Liu, X.; Yu, Y.; Chen, C.; Xiong, Y.; Liu, Y.; Sun, Y.; Tan, C.; Zhang, H.; Wang, Y.; Li, R. miR-502-5p affects gastric cancer progression by targeting PD-L1. Cancer Cell Int., 2020, 20(1), 395.
[http://dx.doi.org/10.1186/s12935-020-01479-2] [PMID: 32821248]
[31]
Ying, Y.; Li, J.; Xie, H.; Yan, H.; Jin, K.; He, L.; Ma, X.; Wu, J.; Xu, X.; Fang, J.; Wang, X.; Zheng, X.; Liu, B.; Xie, L. CCND1, NOP14 and DNMT3B are involved in miR-502-5p-mediated inhibition of cell migration and proliferation in bladder cancer. Cell Prolif., 2020, 53(2), e12751.
[http://dx.doi.org/10.1111/cpr.12751] [PMID: 31971654]
[32]
Zhang, H. CCND1 silencing suppresses liver cancer stem cell differentiation through inhibiting autophagy. Hum. Cell, 2020, 33(1), 140-147.
[http://dx.doi.org/10.1007/s13577-019-00295-9] [PMID: 31667787]
[33]
Li, K.; Fan, X.; Yan, Z.; Zhan, J.; Cao, F.; Jiang, Y. Circ_0000745 strengthens the expression of CCND1 by functioning as miR-488 sponge and interacting with HuR binding protein to facilitate the development of oral squamous cell carcinoma. Cancer Cell Int., 2021, 21(1), 271.
[http://dx.doi.org/10.1186/s12935-021-01884-1] [PMID: 34020639]
[34]
Yang, Y.; Lu, T.; Li, Z.; Lu, S. FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer. Cell Adhes. Migr., 2020, 14(1), 82-95.
[http://dx.doi.org/10.1080/19336918.2020.1766308] [PMID: 32380883]
[35]
Ding, H.; Wang, Y.; Zhang, H. CCND1 silencing suppresses liver cancer stem cell differentiation and overcomes 5-Fluorouracil resistance in hepatocellular carcinoma. J. Pharmacol. Sci., 2020, 143(3), 219-225.
[http://dx.doi.org/10.1016/j.jphs.2020.04.006] [PMID: 32418739]
[36]
Wang, S.S.; Huang, Z.G.; Wu, H.Y.; He, R.Q.; Yang, L.H.; Feng, Z.B.; Dang, Y.W.; Lu, H.P.; Fang, Y.Y.; Chen, G. Downregulation of miR-193a-3p is involved in the pathogenesis of hepatocellular carcinoma by targeting CCND1. PeerJ, 2020, 8, e8409.
[http://dx.doi.org/10.7717/peerj.8409] [PMID: 32095323]
[37]
Wu, S.Y.; Lan, S.H.; Liu, H.S. Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis. Autophagy, 2019, 15(4), 729-730.
[http://dx.doi.org/10.1080/15548627.2019.1569918] [PMID: 30646811]

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