Hepatitis B virus (HBV) is a major risk factor for the development and progression of
hepatocellular carcinoma (HCC). It has been reported that
viral infection can interfere with the expression of cellular
microRNA (
miRNA) to affect
oncogenesis. In this study, we showed that miR-520c-3p was upregulated in liver
tumor specimens, and we revealed that HBV
infection enhanced the expression of miR-520c-3p through the interaction of
viral protein HBV X protein (HBx) with
transcription factor CREB1. We further showed that miR-520c-3p induced by HBV transfection/
infection caused epithelial-mesenchymal transition (EMT). Using the
miRNA target prediction database miRBase and
luciferase reporter assays, we identified PTEN as a novel target gene of miR-520c-3p and miR-520c-3p directly targeted PTEN's 3'-untranslated region. Moreover, we discovered that HBV promoted EMT via the miR-520c-3p-PTEN to activate AKT-NFκB signaling pathway, leading to increased HCC migration and invasion. Importantly, miR-520c-3p
antagomir significantly represses invasiveness in HBx-induced hepatocellular xenograft models. Our findings indicate that miR-520c-3p is a novel regulator of HBV and plays an important role in HCC progression. It may serve as a new
biomarker and molecular therapeutic target for HBV patients.