MiR-340-5p: a potential direct regulator of Nrf2 expression in post-exercise skeletal muscle of mice

Article

Mei, Tao, Liu, Yujia, Wang, Jianxiong and Zhang, Ying. 2019. "MiR-340-5p: a potential direct regulator of Nrf2 expression in post-exercise skeletal muscle of mice." Molecular Medicine Reports. 19 (2), pp. 1340-1348. https://doi.org/10.3892/mmr.2018.9762
Article Title

MiR-340-5p: a potential direct regulator of Nrf2 expression in post-exercise skeletal muscle of mice

ERA Journal ID211112
Article CategoryArticle
AuthorsMei, Tao (Author), Liu, Yujia (Author), Wang, Jianxiong (Author) and Zhang, Ying (Author)
Journal TitleMolecular Medicine Reports
Journal Citation19 (2), pp. 1340-1348
Number of Pages9
Year2019
Place of PublicationGreece
ISSN1791-2997
1791-3004
Digital Object Identifier (DOI)https://doi.org/10.3892/mmr.2018.9762
Web Address (URL)https://www.ncbi.nlm.nih.gov/pubmed/30569154
Abstract

Nuclear factor erythroid 2 -related factor 2 (Nrf2) is a key transcription factor that plays a critical role in handling adaptation to cellular stress induced by exercise. Effects of exercise training on Nrf2 expression have been largely studied, however, the post-transcriptional/translational based regulation of Nrf2 is less understood. The aim of this study was to screen and identify the exercise-induced microRNAs (miRNAs) targeting Nrf2. Twenty C57BL/6J mice were divided into the control (n=10) and exercise groups (n=10). After eight weeks of aerobic exercise training, Nrf2 mRNA in the hind-limb muscles was increased significantly in exercise group, while Nrf2 protein level remained unchanged. 58 differentially expressed miRNAs have been detected; among them, miR-101a-3p and miR-340-5p were predicted to target the 3’ untranslated region (3’UTR) of Nrf2 mRNA, consistently by 3 bioinformatics software. Binding affinity of the two miRNAs were verified via dual luciferase reporter assay, and only miR-340-5p was verified to bind directly to Nrf2 mRNA. Additionally, miR-340-5p mimics and inhibitors were transfected into C2C12 cells to investigate the endogenous biological function of miR-340-5p on the expression of Nrf2. The results showed that the level of Nrf2 protein in C2C12 cells was decreased significantly in the miR-340-5p mimics group and increased significantly in the miR-340-5p inhibitors group, while Nrf2 mRNA remained unchanged, confirming that miR-340-5p plays a role in post-transcriptional control of Nrf2 expression. In conclusion, the novel findings of our study were that the miR-340-5p was a potential direct regulator of Nrf2 gene expression and might be involved in the regulation of Nrf2 protein expression in mouse skeletal muscles following aerobic exercise. These findings reveal the underlying mechanisms of aerobic exercise on Nrf2 protein in skeletal muscle.

Keywordsnuclear factor erythroid 2‑related factor 2, microRNA‑340‑5p, exercise training, skeletal muscle, mice
ANZSRC Field of Research 2020320225. Sports medicine
310111. Signal transduction
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Byline AffiliationsBeijing Sport University, China
School of Health and Wellbeing
Institution of OriginUniversity of Southern Queensland
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