MicroRNA‑34a induces apoptosis in PC12 cells by reducing B‑cell lymphoma 2 and sirtuin‑1 expression

Mol Med Rep. 2015 Oct;12(4):5709-14. doi: 10.3892/mmr.2015.4185. Epub 2015 Aug 5.

Abstract

MicroRNA‑34a (miR‑34a) is a direct target of p53 and was reported to induce cell cycle arrest, apoptosis and senescence. Inhibition of the NAD‑dependent deacetylase sirtuin‑1 (SIRT1) by miR‑34a leads to an increase in acetylated p53, which promotes cell apoptosis. B‑cell lymphoma 2 (Bcl‑2) is also involved in apoptosis, and was originally characterized with respect to its role in controlling outer mitochondrial membrane integrity. The effect of miR‑34a in PC12 cells has not yet been reported. In the present study, it was hypothesized that Bcl‑2 and SIRT1 may be critical downstream targets of miR‑34a that participate in apoptosis induction. miR‑34a mimics and inhibitors were transfected into PC12 cells, and the apoptosis and proliferation rates were compared between groups. It was demonstrated that induction of miR‑34a promotes apoptosis and senescence, inhibits proliferation, and leads to marked alterations in SIRT1, Bcl‑12 and acetyl (ac)‑p53 expression. These data indicate that miR‑34a may be important in neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis / genetics*
  • Cell Proliferation
  • Cellular Senescence
  • Gene Expression Regulation
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Signal Transduction
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transfection
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • MIRN34 microRNA, rat
  • MicroRNAs
  • Oligonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Sirt1 protein, rat
  • Sirtuin 1