MiR-146a regulates SOD2 expression in H2O2 stimulated PC12 cells

PLoS One. 2013 Jul 23;8(7):e69351. doi: 10.1371/journal.pone.0069351. Print 2013.

Abstract

SOD2 (superoxide dismutase 2) is one of the endogenous antioxidant enzymes that protect against reactive oxygen species. While explorations of SOD2 expression regulation are mainly focused on transcriptional and post-translational activation, there are few reports about the post-transcriptional regulation of SOD2. MicroRNAs (miRNAs) are 21nt-25nt (nucleotide) small noncoding RNAs that have emerged as indispensable regulators of gene expression. Here we show that miR-146a, a widely expressed miRNA, is up-regulated by H2O2-induced stress. By sequence analysis we found a binding site for miR-146a in the sod2 mRNA 3'UTR, and a luciferase reporter assay confirmed that miR-146a can interact with this sod2 regulatory region. Our results further show that miR-146a could down-regulate the SOD2 protein expression, and antisense-miR-146a could reverse the decrease of both the SOD2 level and cell viability in H2O2 treated PC12 cells. In conclusion, here we have identified a novel function of miR-146a in the post-transcriptional regulation of SOD2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • PC12 Cells
  • RNA, Antisense / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN146 microRNA, rat
  • MicroRNAs
  • RNA, Antisense
  • RNA, Messenger
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • superoxide dismutase 2

Grants and funding

This work was supported by the National Science and Techology Major Project (2012ZX09J12201), the National Key Techology R&D Program of China (2009BAK59B01), the Medicinal Science and Techology Research Project (BWS11J052), the National Natural Science Foundation of China (30973686), and the Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center(SMFA10B01, SMFA12B05, SMFA09A06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.