期刊
HUMAN GENE THERAPY
卷 31, 期 23-24, 页码 1274-1287出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2020.106
关键词
taurine upregulated gene 1; Parkinson's disease; SH-SY5Y; miR-152-3p; phosphatase and tensin homologue
资金
- Science and Technology Department of Henan Province [152102310356]
Long-noncoding RNAtaurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism ofTUG1in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+)in vitroand mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)in vivo. The expressions ofTUG1,miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction betweenTUG1andmiR-152-3pwas analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model,TUG1expression was upregulated and that ofmiR-152-3pwas downregulated. Further research showed thatTUG1sponged and regulatedmiR-152-3pexpression. Silencing ofTUG1not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammationin vitro, pathological damage and neuroinflammationin vivo, but also suppressed the expressions ofPTENand cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by themiR-152-3pinhibitor. Thus, knocking downTUG1might have a protective effect on PD through themiR-152-3p/PTENpathway.
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