Upregulation of miR-520c-3p via hepatitis B virus drives hepatocellular migration and invasion by the PTEN/AKT/NF-κB axis
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 upregula...
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Published in | Molecular therapy. Nucleic acids Vol. 29; pp. 47 - 63 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
13.09.2022
American Society of Gene & Cell Therapy |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally |
ISSN: | 2162-2531 2162-2531 |
DOI: | 10.1016/j.omtn.2022.05.031 |