<i>Long-Noncoding RNA TUG1</i> Promotes Parkinson's Disease via Modulating <i>MiR-152-3p/PTEN</i> Pathway

Abstract

<i>Long-noncoding RNA</i> taurine upregulated gene 1 (<i>TUG1</i>) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of <i>TUG1</i> in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP⁺) <i>in vitro</i> and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) <i>in vivo</i>. The expressions of <i>TUG1</i>, <i>miR-152-3p</i>, phosphatase and tensin homologue (<i>PTEN</i>), 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 between <i>TUG1</i> and <i>miR-152-3p</i> was 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, <i>TUG1</i> expression was upregulated and that of <i>miR-152-3p</i> was downregulated. Further research showed that <i>TUG1</i> sponged and regulated <i>miR-152-3p</i> expression. Silencing of <i>TUG1</i> not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation <i>in vitro</i>, pathological damage and neuroinflammation <i>in vivo</i>, but also suppressed the expressions of <i>PTEN</i> and 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 the <i>miR-152-3p</i> inhibitor. Thus, knocking down <i>TUG1</i> might have a protective effect on PD through the <i>miR-152-3p/PTEN</i> pathway.