HBeAg-induced miR-106b promotes cell growth by targeting the retinoblastoma gene

Abstract

Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC). The association between hepatitis B “e” antigen (HBeAg) and HCC is well-established by epidemiological studies. Nonetheless, the biological role of HBeAg in HCC remains enigmatic. We investigate the role of HBeAg in HBV-related HCC. Our findings suggest that HBeAg enhances cell proliferation and accelerates progression from G0/G1 phase to the S phase of the cell cycle in Huh7 cells. Examination of host gene expression and miRNA expression profiles reveals a total of 21 host genes and 12 host miRNAs that were differentially regulated in cells expressing HBeAg. Importantly, HBeAg induced the expression of miR-106b, an oncogenic miRNA. Interestingly, HBeAg-expression results in a significant reduction in the expression of retinoblastoma (Rb) gene, an experimentally validated target of miR-106b. Inhibition of miR-106b significantly increased the expression of the Rb gene, resulting in reduced cell proliferation and slowing of cell cycle progression from the G0/G1 phase to S phase. These observations suggest that the up-regulation of miR-106b by HBeAg contributes to the pathogenesis of HBV-related HCC by down-regulating the Rb gene. Our results highlight a role for HBeAg in HCC and provide a novel perspective on the molecular mechanisms underlying HBV-related HCC.

miR-106b targets DAB2 to promote hepatocellular carcinoma cell proliferation and metastasis

“…Although the abnormal expression of miRNAs in HCC was regarded as a cause of HCC, we need to further explore the potential mechanism of the impact of miRNA on the progression of HCC. Previous findings showed that miRNA-106b expression is obviously increased in HCC and may provide a new biomarker for the early diagnosis of HCC ( 18 ). Those findings are in line with those of our study showing that miR-106b was overexpressed in HCC tissues and cells.…”

“…Furthermore, a recent study has shown that in the progression of cervical cancer, DAB2 was confirmed as a target of miR-106b ( 17 ). Another recent study showed that miRNA-106b expression was markedly increased and regulated HCC development by targeting mRNA ( 18 , 19 ). However, whether miR-106b targeted DAB2 in the regulation of HCC progression has yet to be reported.…”

Factors associated with disease progression and viral replication in patients with chronic hepatitis B virus infection

“…HBeAg is a soluble protein in the core particles of HBV, which is processed from the precore protein (27). A number of studies have reported that HBeAg serves a critical role in chronic HBV infection treatment, prognosis and disease progression (28,29). Patients with seropositive HBeAg have an increased risk to develop cirrhosis and HCC.…”

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

“…Then five of these miRNAs were selected for qRT‐PCR validation in a larger cohort, and four of them showed similar expression pattern as those revealed by sequencing data, which indicated a low false discovery rate of our sequencing data and supported the credibility of the profile. Among these differentially expressed miRNAs, hsa‐miR‐99b‐3p, ‐451a, ‐15b‐5p, ‐25‐3p, ‐92a‐3p, ‐106b‐3p, ‐1‐3p, and ‐30a‐5p were also differentially expressed in other stages of HBV infection.…”