LincRNA-p21 Inhibits Cell Viability and Promotes Cell Apoptosis in Parkinson’s Disease through Activatingα-Synuclein Expression

Xiaonan Xu,Hongyan Qiu,Zimu Wu,Haixia Feng,Chengle Zhuang,Jun Wu

doi:10.1155/2018/8181374

Xiaonan Xu, Hongyan Qiu + Show 4 more

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https://doi.org/10.1155/2018/8181374

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Abstract

Long intergenic noncoding RNA-p21 (lincRNA-p21) has been reported to be increased in Parkinson's disease (PD). However, the function and underlying mechanisms of lincRNA-p21 remain not clear. In order to explore the role of lincRNA-p21 in PD, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce in vivo PD model (C57BL/6 mice) and utilized N-methyl-4-phenylpyridinium (MPP+) to create in vitro PD model (SH-SY5Y cells). Results showed that the expression level of lincRNA-p21 was increased significantly in PD models. High abundance of lincRNA-p21 inhibited viability and promoted apoptosis markedly in SH-SY5Y cells treated with MPP+. Mechanistically, further experiments demonstrated that upregulation of lincRNA-p21 could sponge miR-1277-5p and indirectly increase the expression of α-synuclein to suppress viability and activate apoptosis in SH-SY5Y cells. In short, our study illustrated that lincRNA-p21/miR-1277-5p axis regulated viability and apoptosis in SH-SY5Y cells treated with MPP+ via targeting α-synuclein. LincRNA-p21 might be a novel target for PD.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disease owing to a reduction in dopaminergic neurons in the substantia nigra [1, 2]
We investigate the effect of lincRNA-p21 on cell viability and apoptosis in PD model cells (SHSY5Y) treated with N-methyl-4-phenylpyridinium (MPP+)
After knockdown of lincRNA-p21 in SHSY5Y cells treated with MPP+, cell viability was increased remarkably compared with the si-NC+ MPP+ group (P < 0.01)

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disease owing to a reduction in dopaminergic neurons in the substantia nigra [1, 2]. Bradykinesia, depression, anxiety, static tremors, and cognitive dysfunction are typical symptoms of PD [4] Various factors such as heredity, environment, and life style are closely related to the occurrence of PD, and the prevalence of PD all over the world is 1-2% of populations among populations over 65 years of age [5, 6]. Long noncoding RNAs (lncRNAs) with length of more than 200 nucleotides are involved in various biological processes, such as tumor development, transcriptional regulation, and cell apoptosis [8]. Long intergenic noncoding RNA-p21 (lincRNA-p21), 3100 nt, is located on chromosome 6, involved in cell proliferation, metabolism, and reprogramming, and regarded as a potential diagnostic marker in various diseases [9]. LincRNA-p21 can activate hepatic stellate cells through lincRNA-p21-miR-181b-PTEN pathway in liver

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