HBx Down-Regulated Gld2 Plays a Critical Role in HBV-Related Dysregulation of miR-122

Abstract

miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2.

HBx promotes cell proliferation by disturbing the cross-talk between miR-181a and PTEN

“…To gain insight into the biological role of HBx in miRNA expression pattern, we analyzed the expression of miR-181a in human HepG2 cells transfected with HBs, HBc, HBp and HBx vector, respectively12. We found that HBx was the only protein encoded by HBV that promoted miR-181a expression (Fig.…”

Downregulation of MicroRNA-145 Caused by Hepatitis B Virus X Protein Promotes Expression of CUL5 and Contributes to Pathogenesis of Hepatitis B Virus-Associated Hepatocellular Carcinoma

“…In this study, we performed real-time PCR on tumor tissue samples collected from 53 HCC patients (25 HBV-positive cases and 28 HBV-negative cases) to screen the candidate miRNAs that have previously been reported to be aberrantly expressed in HBV-associated HCC [27], including miR-152, -143, -192, -19b, -18b, -148a, -345, -145, -122, -210, -18a and -20b. This was performed to identify the miRNA and its target gene(s) that mediate …”

“…miRNAs have recently been reported to mediate HBX-induced cell proliferation and invasion in HCC [22][23][24][25][26]. Peng et al reported on differentially expressed miRNAs using a microarray analysis of the expression profiles of HepG2 and HepG2.2.15 cells, which represent a well-known HBX-secreting HCC cell line [27]. In this study, we screened the candidate miRNAs that were previously reported to be aberrantly expressed [27] to identify the miRNA (and its target gene(s)) that mediate the effect of HBX in HCC development.…”

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“…Hepatocellular carcinoma (HCC) is the fifth most frequent solid tumour and the third leading cause of cancer deaths worldwide (55)(56)(57)(58). Chronic infection with either hepatitis B or C virus plays significant roles in the development of HCC (59)(60)(61). Despite recent advances in surgery and medical treatment, the prognosis of HCC patients remains extremely poor (62)(63)(64).…”