Inhibition of miR-148a-3p resists hepatocellular carcinoma progress of hepatitis C virus infection through suppressing c-Jun and MAPK pathway

J Cell Mol Med. 2019 Feb;23(2):1415-1426. doi: 10.1111/jcmm.14045. Epub 2018 Dec 18.

Abstract

Objectives: The present study was committed to investigate the role of miR-148a-3p in HCC infected with hepatitis C virus (HCV) and the regulatory mechanism of miR-148a-3p/c-Jun/MAPK signalling pathway.

Methods: Differential analysis and GSEA analysis were performed with R packages. QRT-PCR and Western blot were used to detect RNA or protein level, respectively. The targeted relationship between miR-148a-3p and c-Jun was predicted by TargetScan database and determined by double luciferase reporter assay. MTT assay and flow cytometry were used to evaluate cell proliferation, cell cycle and cell apoptosis, respectively.

Results: C-Jun was up-regulated, and MAPK signalling pathway was activated in HCV-infected HCC cells. C-Jun expression regulated inflammation-related gene expression and had an influence on cell proliferation, cell cycle and cell apoptosis. MiR-148a-3p, down-regulated in HCV-infected HCC cells, could target c-Jun mRNA to suppress c-Jun protein expression.

Conclusions: MiR-148a-3p suppressed the proliferation of HCC cells infected with HCV through targeting c-Jun mRNA.

Keywords: c-Jun; MAPK signalling pathway; hepatitis C virus; hepatoma; miR-148a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Cycle / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C / genetics*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • MAP Kinase Signaling System / genetics
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics
  • RNA, Messenger / genetics

Substances

  • MIRN148 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Messenger
  • JNK Mitogen-Activated Protein Kinases