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

  • Caggiano R
  • Cattaneo F
  • Moltedo O
  • et al.
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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.

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Caggiano, R., Cattaneo, F., Moltedo, O., Esposito, G., Perrino, C., Trimarco, B., … Faraonio, R. (2017). miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells. Oxidative Medicine and Cellular Longevity, 2017, 1–13. https://doi.org/10.1155/2017/9308310

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