Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a

Abstract

RAB GTPase 5A (RAB5A), a member of the Rab subfamily of small GTPases, acts as an oncogene and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Recently, it has been reported that the Rab5a gene is involved in the progression of cancer. Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers, and it is usually associated with persistent hepatitis B virus (HBV) infections. Emerging evidence suggests that HBV alters microRNA (miRNA) expression profiles, but the mechanisms underlying this process have not yet been fully elucidated. Here, we examine how HBV affects the production of miR-101-1, which has been shown to be downregulated in HCC. We found that HBV could repress miR-101-3p by inhibiting its promoter activity. Downregulation of miR-101-3p promoted cancer cell growth and migration, and a specific miR-101-3p inhibitor was able to enhance proliferation and migration. Moreover, we identified Rab5a was one of the target genes of miR-101-3p in HBV-related HCC. Forced expression of miR-101-3p in liver cell lines resulted in a marked reduction of the expression of Rab5a at both the mRNA and protein level by directly targeting the 3'untranslated region of Rab5a. Overexpression of Rab5a resulted in a reversal of the suppression of proliferation and migration of SMMC-7721 cells mediated by miR-101-3p. Taken together, our data show that HBV can downregulate miR-101-3p expression by inhibiting its promoter activity and that downregulation of miR-101-3p promotes HCC cell proliferation and migration by targeting Rab5a. This provides new insights into the mechanisms of HBV-related HCC pathogenesis.

MicroRNA-26b-5p regulates cell proliferation, invasion and metastasis in human intrahepatic cholangiocarcinoma by targeting S100A7

“…In order to identify novel biomarkers for ICC, 5 candidate miRNAs (miR-101-3p, miR-147a, miR-196-5p, miR-93-3p and miR-26b-5p), which have been associated with other types of cancer and diseases (16)(17)(18)(19)(20), were quantified in RBE, iRBE, HCCC-9810 and iHCCC-9810 cells with RT-qPCR. As presented in Fig.…”

MicroRNA-101 suppresses migration and invasion via targeting vascular endothelial growth factor-C in hepatocellular carcinoma cells

“…Sheng et al (17) also suggested that miR-101 is involved in the regulation of HCC cell migration. However, the molecular mechanism underlying the effect of miR-101 on HCC cell migration and invasion remains to be fully elucidated.…”

Integrated Analysis of miRNA and Gene Networks on Cancer Expression Data

“…TABLE VI shows top ten results with the significant pearson score. Among the miRNAs, downregulation of MIMAT0000099 (hsa-miR-101-3p) promoted cancer cell growth and migration, and Rab5a is one of the target genes of miR-101-3p in LIHC [38]. [39].…”