Downregulation of Bcl-2 expression by miR-34a mediates palmitate-induced Min6 cells apoptosis

J Diabetes Res. 2014:2014:258695. doi: 10.1155/2014/258695. Epub 2014 Apr 14.

Abstract

Recent studies have demonstrated that the expression of miR-34a is significantly upregulated and associated with cell apoptosis in pancreatic β -cell treated with palmitate. Nevertheless, the underlying detailed mechanism is largely unknown. Here, we showed that miR-34a was significantly induced in Min6 pancreatic β -cell upon palmitate treatment. Elevated miR-34a promoted Min6 cell apoptosis. Intriguingly, ectopic expression of miR-34a lowered the expression of Bcl-2, an antiapoptotic protein. Luciferase reporter assay indicated the direct interaction of miR-34a with the Bcl-2 3'-UTR. Moreover, downregulated expression of Bcl-2 induced by palmitate could be restored by inhibition of miR-34a. We conclude that direct suppression of Bcl-2 by miR-34a accounts for palmitate-induced increased apoptosis rate in pancreatic β -cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis*
  • Caspase 3 / chemistry
  • Caspase 3 / metabolism
  • Cell Line
  • Down-Regulation*
  • Fatty Acids, Nonesterified / metabolism*
  • Gene Expression Regulation
  • Gene Silencing
  • Genes, Reporter
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / enzymology
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Mutagenesis, Site-Directed
  • Mutation
  • Palmitic Acid / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Fatty Acids, Nonesterified
  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Recombinant Proteins
  • Bcl2 protein, mouse
  • Palmitic Acid
  • Casp3 protein, mouse
  • Caspase 3