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

Mei, Tao and Liu, Yujia and 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. ISSN 1791-2997


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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to Published version in accordance with the copyright policy of the publisher.
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing
Date Deposited: 01 Jul 2019 05:19
Last Modified: 04 Jul 2019 00:54
Uncontrolled Keywords: nuclear factor erythroid 2‑related factor 2, microRNA‑340‑5p, exercise training, skeletal muscle, mice
Fields of Research : 11 Medical and Health Sciences > 1106 Human Movement and Sports Science > 110604 Sports Medicine
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction
Identification Number or DOI: 10.3892/mmr.2018.9762
URI: http://eprints.usq.edu.au/id/eprint/35504

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