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

Area of Science:

• Molecular Biology
• Gene Regulation
• Cellular Stress Response

Background:

• Small MAF (sMAF) proteins, including MAFG, are bZIP transcriptional regulators that form dimers to control gene expression.
• MAFG, as a partner of Nrf2, modulates antioxidant and xenobiotic pathways via the ARE.
• The role of microRNAs (miRs) in regulating stress response pathways involving MAFG and Nrf2 is not well understood.

Purpose of the Study:

• To investigate the impact of miR-128 on gene expression related to cellular stress response.
• To determine if MAFG is a direct target of miR-128.
• To elucidate the functional consequences of miR-128 regulation on MAFG-Nrf2 mediated pathways.

Main Methods:

• Bioinformatic prediction of miR-128 binding sites in MAFG 3'UTR.
• Functional analysis including ectopic miR-128 expression.
• Assessment of MAFG-dependent gene expression and ARE-mediated Nrf2 activity.
• Analysis of gene expression (HMOX-1, x-CT) under hypoxia.

Main Results:

• miR-128 directly binds to the 3'UTR of MAFG mRNA.
• Ectopic miR-128 expression reduces MAFG-dependent gene expression and impairs Nrf2/ARE activity.
• miR-128 negatively affects redox-dependent pathways during oxidative stress.
• Hypoxia induces MAFG, which correlates with reduced miR-128, leading to increased HMOX-1 and x-CT expression.

Conclusions:

• MAFG is identified as a novel direct target of miR-128.
• miR-128 negatively regulates MAFG expression and its role in ARE-mediated stress response.
• This study reveals a new layer of microRNA-mediated control over cellular surveillance to stress.