2. Academic Validation
  3. Upregulation of miR-520c-3p via hepatitis B virus drives hepatocellular migration and invasion by the PTEN/AKT/NF-κB axis

Upregulation of miR-520c-3p via hepatitis B virus drives hepatocellular migration and invasion by the PTEN/AKT/NF-κB axis

  • Mol Ther Nucleic Acids. 2022 May 20:29:47-63. doi: 10.1016/j.omtn.2022.05.031.
Yang Liu 1,  Jingwen Wang 1,  Jianwen Chen 1,  Shaoshuai Wu 1,  Xianhuang Zeng 1,  Qiushuang Xiong 1,  Yandan Guo 1,  Junwei Sun 2,  Feifei Song 1,  Jiaqi Xu 1,  Sen Yuan 1,  Chuang Li 1 3,  Yuan He 1,  Ming Wang 4,  Lang Chen 1,  Yun-Bo Shi 5,  Mingxiong Guo 3 6,  Deyin Guo 1 7,  Guihong Sun 1 8
Affiliations

Affiliations

  • 1 Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, Hubei, P.R. China.
  • 2 Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, Wuhan 430079, Hubei, P.R. China.
  • 3 Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, P.R. China.
  • 4 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China.
  • 5 Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • 6 Ecological Research Center, College of Science, Tibet University, Lhasa 850012, Tibet, P.R. China.
  • 7 School of Medicine, Sun Yat-Sen University, Guangzhou 510000, Guangdong, P.R. China.
  • 8 Hubei Provincial Key Laboratory of Allergy and Immunology, Wuhan 430071, Hubei, P.R. China.
PMID: 35795482 DOI: 10.1016/j.omtn.2022.05.031
Abstract

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.

Keywords

HBV/HBx; MT: non-coding RNAs; NF-κB; PTEN; hepatocellular carcinoma; miR-520c-3p; migration and invasion.

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