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Overexpression of MicroRNA-133a Inhibits Apoptosis and Autophagy in a Cell Model of Parkinson’s Disease by Downregulating Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1)

Wusheng Lu, Jinhuang Lin, Dequan Zheng, Chunyong Hong, Laishun Ke, Xinyu Wu, Peineng Chen

Department of Neurology, The 909th Hospital of (People’s Liberation Army) PLA, Zhangzhou, Fujian, China (mainland)

Med Sci Monit 2020; 26:e922032

DOI: 10.12659/MSM.922032

Available online: 2020-05-29

Published: 2020-07-27

BACKGROUND: Parkinson’s disease (PD) is a movement disorder. microRNA (miR)-133 expression is reduced in PD patients and in mice with a dopamine neuron deficiency. We aimed to identify the mechanism of miR-133a in apoptosis and autophagy in PD.
MATERIAL AND METHODS: The optimal concentration of MPP⁺ (1-methyl-4-phenylpyridinium ion) was initially determined to construct a PD cell model. Gain-of function experiments were carried out to evaluate the role of miR-133a in PD. The levels of miR-133a, RAC1 (Ras-related C3 botulinum toxin substrate 1), apoptosis-related factors, and autophagy-related factors were detected after detection of cell proliferation, cell cycle, and apoptosis. Transmission electron microscopy was applied to observe autophagosomes, and immunofluorescence staining was performed to detect LC3 and further analyze the effect of miR-133a on autophagy in a PD cell model.
RESULTS: Low miR-133a expression was detected in a cell model of MPP⁺-induced PD. After overexpressing miR-133a, cell proliferation increased, and apoptosis (cleaved caspase-3 and Bax levels decreased, while Bcl2 levels increased) and autophagy was inhibited (LC3II/I and Beclin-1 levels decreased, while p62 levels increased). MiR-133a targeted RAC1. RACY upregulation attenuated the inhibitory effects of miR-133a on PC12 cell apoptosis and autophagy.
CONCLUSIONS: Our data highlighted that miR-133a overexpression prevented apoptosis and autophagy in a cell model of MPP⁺-induced PD by inhibiting RAC1 expression.

Keywords: Apoptosis, Autophagy, MicroRNAs, Parkinson Disease