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Research Paper|Volume 13, Issue 1|pp 1369—1382

MicroRNA-6862 inhibition elevates sphingosine kinase 1 and protects neuronal cells from MPP+-induced apoptosis

Gang Xue1,2, Ju-ping Chen3, Ya Li4, Zhi-qing Zhang5, Jian-liang Zhu6, Wanli Dong1
  • 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China
  • 2Department of Neurology, Fengcheng Hospital of Fengxian Distric, Shanghai, China
  • 3Department of Neurology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
  • 4The Central Laboratory, North District, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, China
  • 5Institute of Neuroscience, Soochow University, Suzhou, China
  • 6Department of Emergency and Intensive Care Unit, The Second Affiliated Hospital of Soochow University, Suzhou, China
* Equal contribution
Received: September 3, 2020Accepted: October 22, 2020Published: December 19, 2020
https://doi.org/10.18632/aging.202335

Copyright: © 2020 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

MPP+ (1-methyl-4-phenylpyridinium)-induced dopaminergic neuronal cell apoptosis is associated with sphingosine kinase 1 (SphK1) inhibition. We here tested the potential effect of microRNA-6862 (miR-6862), a novel SphK1-targeting miRNA, on MPP+-induced cytotoxicity in neuronal cells. MiR-6862 locates in the cytoplasm of SH-SY5Y neuronal cells. It directly binds to SphK1 mRNA. In SH-SY5Y cells and HCN-2 cells, ectopic overexpression of miR-6862 decreased SphK13’-untranslated region luciferase reporter activity and downregulated its expression. miR-6862 inhibition exerted opposite activity and elevated SphK1 expression. In neuronal cells, MPP+-induced cell death was significantly inhibited through miR-6862 inhibition. Conversely, ectopic overexpression of miR-6862 or CRISPR/Cas9-induced SphK1 knockout augmented MPP+-induced apoptosis in the neuronal cells. Importantly, antagomiR-6862 failed to inhibit MPP+-induced apoptosis in SphK1-knockout SH-SY5Y cells. These results suggest that inhibition of miR-6862 induces SphK1 elevation and protects neuronal cells from MPP+-induced cell death.