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SOX21-AS1 modulates neuronal injury of MMP+-treated SH-SY5Y cells via targeting miR-7-5p and inhibiting IRS2
Neuroscience Letters ( IF 2.5 ) Pub Date : 2021-01-06 , DOI: 10.1016/j.neulet.2020.135602
Yang Xie , Shujiang Zhang , Zhiyu Lv , Ting Long , Ying Luo , Zuoxiao Li

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.



中文翻译:

SOX21-AS1通过靶向miR-7-5p和抑制IRS2调节MMP +处理的SH-SY5Y细胞的神经元损伤

由黑质中多巴胺能神经元数量减少引起的帕金森氏病(PD)被确定为公众第二大最熟悉的年龄依赖性神经退行性疾病。据报道,长的非编码RNA(lncRNA)参与PD的发展。在我们的研究中,lncRNA SRY-box转录因子21反义分歧转录本1(SOX21-AS1)的表达在1-甲基-4-苯基吡啶(MMP +)处理的SH-SY5Y细胞中上调。此外,SOX21-AS1耗竭减弱了MMP +诱导的细胞损伤。此外,SOX21-AS1组合物减少了活性氧(ROS)的生成以及TNF-α,IL-1β和IL-6的水平,但增加了SOD活性。但是,SOX21-AS1的上调导致相反的结果。此外,SOX21-AS1可以与miR-7-5p结合,miR-7-5p的过表达缓解了MMP +诱导的细胞损伤。此外,胰岛素受体底物2(IRS2)作为miR-7-5p的靶基因,其表达受到SOX21-AS1的正调控。同样,IRS2抑制对MMP +治疗刺激的细胞损伤也具有缓解作用。总而言之,我们的研究表明SH-SY5Y细胞中由SOX21-AS1,miR-7-5p和IRS2组成的新调控网络,对PD的致病机理提供了更好的理解。

更新日期:2021-01-28
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