Pterostilbene increases PTEN expression through the targeted downregulation of microRNA-19a in hepatocellular carcinoma

Mol Med Rep. 2018 Apr;17(4):5193-5201. doi: 10.3892/mmr.2018.8515. Epub 2018 Jan 29.

Abstract

Pterostilbene (Pter) is reported to exhibit an anticancer effect in hepatocellular carcinoma (HCC). In order to explore the anticancer mechanism in HCC cells, the present study aimed to investigate whether pterostilbene (Pter) may increase phosphatase and tensin homolog (PTEN) expression through targeted downregulation of microRNA (miRNA/miR)-19a in hepatocellular carcinoma (HCC). The proliferation, apoptosis and cell cycle was analyzed in the SMMC‑7721 HCC cell line by MTT assays and flow cytometry methods. Cells were divided into five treatment groups: Pter treatment, miR‑19a inhibitor transfection, Pter + miR‑19a inhibitor, negative control transfection and blank control. The expression of miR‑19a and PTEN was detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis following treatment. Furthermore, a luciferase reporter gene assay was performed to determine whether the PTEN gene was a direct target of miR‑19a. The results demonstrated that Pter treatment or miR‑19a inhibitor transfection downregulated miR‑19a and induced PTEN/Akt pathway regulation, which led to proliferation inhibition, cell cycle arrest in the S phase, increased apoptosis and reduced cell invasion. These results indicated that Pter may increase PTEN expression through the direct downregulation of miR‑19a in HCC. Therefore, miR‑19a may have potential as a novel molecular marker for HCC and Pter may be a promising clinical target with the potential to be developed as a HCC therapy.

Keywords: phosphatase and tensin homolog; Akt; microRNA-19a; pterostilbene; hepatocellular carcinoma.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, Reporter
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • RNA Interference*
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*

Substances

  • 3' Untranslated Regions
  • MIRN19 microRNA, human
  • MicroRNAs
  • Stilbenes
  • pterostilbene
  • PTEN Phosphohydrolase
  • PTEN protein, human