Contribution of hepatitis B virus X protein-induced aberrant microRNA expression to hepatocellular carcinoma pathogenesis

Abstract

The hepatitis B virus-encoded X (HBX) protein plays important roles in Hepatocellular carcinoma (HCC). Previous studies have demonstrated that HBX can induce alterations in the expression of numerous microRNAs (miRNAs) involved in the carcinogenesis of various tumors. However, the global profile of liver miRNA changes induced by HBX has not been characterized. In this study, we conducted a miRNA microarray analysis to investigate the influence of HBX on the expression of total miRNAs in liver in relation to HCC. Comparative analysis of the data from human normal liver cells (L02) and human HCC cells (HepG2), with or without HBX, identified 19 differentially expressed miRNAs, including 5 with known association to HBX. Target gene prediction for the aberrantly expressed miRNAs identified a total of 304 potential target genes, involved in sundry pathways. Finally, pathway analysis of the HBXinduced miRNAs pathway showed that 5 of the total miRNAs formed an internetwork, suggesting that HBX might exert its pathological effects on hepatic cells through functional synergy with miRNAs that regulated common pathways in liver cells. Therefore, this work provides new insights into the mechanisms of HCC as well as potential diagnostic markers or therapeutic targets for use in clinical management of HCC.

Hepatitis B virus X protein induces expression changes of miR-21, miR-22, miR-122, miR-132, and miR-222 in Huh-7 cell line

“…In HBx-induced HCC, signaling pathways that control the normal physiological functions of the host cells are disrupted. For instance, HBx protein can modify the expression of microRNAs (miRNAs), which has been demonstrated to contribute to HCC pathogenesis (5). The miRNAs can affect the expression of oncogenes or tumor-suppressor genes.…”

“…The inhibiting effect of miRNA-205 on carcinogenesis was also shown to be reduced by HBx through decreasing miRNA-205 expression in the livers of transgenic HBx mice (8). Although several reports have provided evidence of a relationship between HBx, specific miRNAs, and target genes (5,7), the regulation of the global miRNA profile in liver cells by HBx in relation to the development and progression of HCC remains to be fully clarified. Therefore, this study was designed to investigate the role of HBx in the variation of the gene-expression profiles of miR-21, miR-22, miR-122, miR-132, and miR-222 in the Huh-7 cell line.…”