miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells

Oxid Med Cell Longev. 2017:2017:9308310. doi: 10.1155/2017/9308310. Epub 2017 Sep 12.

Abstract

MAFG (v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) is a bZIP-type transcriptional regulator that belongs to the small MAF (sMAFs) protein family. By interacting with other bZIP transcription factors, sMAFs can form homo- and heterodimers governing either repressive or activating transcriptional functions. As heterodimeric partner of Nrf2, MAFG positively influences the ARE-dependent antioxidant/xenobiotic pathways, at least in condition of a correct MAFG:Nrf2 balance. MicroRNAs (miRs) participate to different regulatory networks being involved as fine-tuning regulators of gene expression. However, the connections between cellular surveillance to stresses mediated by MAFG:Nrf2 and miR regulations are not well understood. Here, we explored the impact of miR-128 in expression of genes related to stress response. Bioinformatic predictions coupled with functional analysis revealed the presence of miR-128 binding site in the 3'UTR of MAFG. Ectopic miR-128 expression correlated with reduced expression of endogenous MAFG-dependent genes and negatively affected ARE-mediated molecular phenotype based on Nrf2 activity. Indeed, miR-128 impairs redox-dependent pathways induced in response to oxidative stress. Moreover, in condition of hypoxia, MAFG induction correlated with reduced levels of miR-128. This lead to increased mRNA levels of HMOX-1 and x-CT for blunting stress. Overall, these findings identify MAFG as novel direct target of miR-128.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antioxidants / metabolism
  • Binding Sites
  • HEK293 Cells
  • Heme Oxygenase-1 / metabolism
  • Humans
  • MafG Transcription Factor / genetics
  • MafG Transcription Factor / metabolism*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle Fibers, Skeletal / metabolism*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / genetics*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Antioxidants
  • MAFG protein, human
  • MIRN128 microRNA, human
  • MafG Transcription Factor
  • Mafg protein, mouse
  • Membrane Proteins
  • MicroRNAs
  • Mirn128 microRNA, mouse
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Nfe2l2 protein, mouse
  • Repressor Proteins
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Hmox1 protein, mouse