MicroRNA-548p suppresses hepatitis B virus X protein associated hepatocellular carcinoma by downregulating oncoprotein HBXIP.

2015 
Abstract MiR-548p is a recently identified and poorly characterized miRNA. However, its role of miR-548p in tumorigenesis and progression remains poorly understood. Here, we aimed to investigate the biofunction of miR-548p in hepatocellular carcinogenesis. The expression levels of miR-548p were detected by qRT-PCR. The role of miR-548p in hepatocellular carcinoma (HCC) was determined by colony formation, flow cytometry assay, and nude mice xenograft experiments. MiR-548p target genes were analyzed by microRNA target predication programs and verified by qRT-PCR, western blotting assay and Dual-Luciferase reporter assay. MiR-548p is repressed by hepatitis B virus X protein (HBx) in HCC tumor tissues and hepatoma cells, and inhibited cell growth by inhibiting cell proliferation and promoting cell apoptosis. MiR-548p directly downregulated the expression of hepatitis B x-interacting protein (HBXIP) by binding to the 3'UTR of HBXIP mRNA. Further study showed that Hepatocyte nuclear factor-4a (HNF4A) promoted the expression of miR-548p and inhibited the transcription of HBXIP. HNF4A is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis, and is shown to be repressed by HBx. We proposed the model for HBx/HNF4A/miR-548p/HBXIP pathway that controls hepatoma cell growth and tumorigenesis of HCC. MiR-548p was identified as a tumor-suppressor in HBx-associated hepatocellular carcinogenesis.
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