SOX21-AS1 modulates neuronal injury of MMP+-treated SH-SY5Y cells via targeting miR-7-5p and inhibiting IRS2.

Abstract:

:Parkinson's disease (PD), caused by the decreased number of dopaminergic neurons in the substantia nigra, is identified as the second most familiar age-dependent neurodegenerative disease to the public. Long non-coding RNAs (lncRNAs) have been reported to participate in the development of PD. In our research, the expression of lncRNA SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) was up-regulated in 1-methyl-4-phenylpyridinium (MMP+)-treated SH-SY5Y cells. In addition, SOX21-AS1 depletion weakened the cell injury induced by MMP+. Moreover, SOX21-AS1 knockdown decreased Reactive Oxygen Species (ROS) generation and levels of TNF-α, IL-1β and IL-6, but increased SOD activity. However, SOX21-AS1 up-regulation led to opposite results. Further, SOX21-AS1 could bind with miR-7-5p, whose overexpression relieved MMP+-induced cell injury. Additionally, insulin receptor substrate 2 (IRS2) served as the target gene of miR-7-5p, and its expression was positively modulated by SOX21-AS1. Similarly, IRS2 knockdown also had alleviative effects on cell injury stimulated by MMP+ treatment. In sum up, our study demonstrated a new regulatory network consisted of SOX21-AS1, miR-7-5p and IRS2 in SH-SY5Y cells, supplying with a better comprehension about the pathogenic mechanism of PD.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Xie Y,Zhang S,Lv Z,Long T,Luo Y,Li Z

doi

10.1016/j.neulet.2020.135602

subject

Has Abstract

pub_date

2021-01-06 00:00:00

pages

135602

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(20)30872-7

pub_type

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