Gene therapy targeting miR‑212‑3p exerts therapeutic effects on MAFLD similar to those of exercise

Sun,Bo; Sun,Bo; Zhang,Yu; Zhang,Yu; Zhang,Minbo; Zhang,Minbo; Liu,Ruilin; Liu,Ruilin; Yang,Wenzhuo; Yang,Wenzhuo

doi:10.3892/ijmm.2023.5219

Gene therapy targeting miR‑212‑3p exerts therapeutic effects on MAFLD similar to those of exercise

Authors:
- Bo Sun
- Yu Zhang
- Minbo Zhang
- Ruilin Liu
- Wenzhuo Yang
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Affiliations: Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China, Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
Published online on: January 11, 2023 https://doi.org/10.3892/ijmm.2023.5219
Article Number: 16
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exercise is the main treatment for patients with metabolic‑associated fatty liver disease (MAFLD); however, it may be difficult for some patients to adhere to or tolerate an exercise regime. Thus, finding a treatment alternative to exercise is of particular importance. The authors have previously demonstrated that the high expression of microRNA (miRNA/miR)‑212 promotes lipogenesis in vitro. The present study aimed to explore the therapeutic potential, as well as the mechanisms of action of miR‑212 in MAFLD. The expression of miR‑212‑3p, but not that of miR‑212‑5p, was found to be significantly elevated in MAFLD and to be decreased by exercise. Compared with exercise treatment, the inhibition of miR‑212‑3p expression in a mouse model fed a high‑fat diet exerted beneficial effects on MAFLD similar to those of exercise. Conversely, the overexpression of miR‑212‑3p abolished the ameliorative effects of exercise on MAFLD. Fibroblast growth factor 21 (FGF21) and chromodomain helicase DNA binding protein 1 (CHD1) were identified as target genes of miR‑212‑3p in lipid metabolism using bioinformatics analysis. Mechanistically, the inhibition of miR‑212‑3p mimicked the effects of exercise on lipid metabolism by regulating FGF21, but not CHD1. The exercise‑related transcription factor, early growth response 1 (EGR1), was identified upstream of miR‑212‑3p through promoter motif analysis. EGR1 overexpression inhibited miR‑212‑3p expression. The overexpression of miR‑212‑3p abolished the effects of exercise on lipid metabolism by exogenously attenuating the transcriptional repression of EGR1. Moreover, the overexpression of miR‑212‑3p abolished the regulatory effects of EGR1 on FGF21. On the whole, the present study demonstrates that miR‑212‑3p plays a key role in the effects of exercise on MAFLD. The findings presented herein suggest a potential therapeutic effect of targeting miR‑212‑3p in MAFLD.

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