microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma

Biomed Pharmacother. 2018 Sep:105:1147-1154. doi: 10.1016/j.biopha.2018.06.097. Epub 2018 Jun 21.

Abstract

microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.

Keywords: Chemoresistance; Hepatocellular carcinoma; Metastasis; microRNA-19a-3p.

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / physiology*
  • Gene Expression Regulation, Neoplastic
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology

Substances

  • MIRN19A microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human