Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

中文翻译：

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SNHG1 通过海绵化 miR-153-3p 调节 SH-SY5Y 细胞中的 PTEN/AKT/mTOR 信号通路促进 MPP+ 诱导的细胞毒性

长链非编码 RNA 小分子 RNA 宿主基因 1 (SNHG1) 先前被确定为与帕金森病 (PD) 发病机制相关。本工作旨在进一步阐明 SNHG1 参与 PD 的调控网络。分别构建了1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐（MPTP）诱导的小鼠和1-甲基-4-苯基吡啶（MPP+）处理的SH-SY5Y细胞作为体内和体外 PD 模型。通过qRT-PCR检测SNHG1和miR-153-3p的表达水平。通过蛋白质印迹测定法测量第十号染色体上缺失的磷酸盐和张力同源性（PTEN）的蛋白质表达水平。通过MTT和流式细胞术测定细胞活力和细胞凋亡。SNHG1、miR-153-3p 和 PTEN 之间的相互作用通过荧光素酶报告基因测定、RNA 免疫沉淀、和/或 RNA 下拉分析。在 MPTP 诱导的 PD 小鼠和 MPP+ 处理的 SH-SY5Y 细胞的中脑中发现 SNHG1 表达增加。SNHG1 的过表达降低了 MPP+ 处理的 SH-SY5Y 细胞的活力并增强了细胞凋亡。此外，SNHG1 作为分子海绵抑制 miR-153-3p 的表达。此外，在 SNHG1 上调后，miR-153-3p 介导的 MPP+ 诱导的细胞毒性抑制减弱。此外，PTEN 被确定为 miR-153-3p 的直接靶标，SNHG1 可以作为 miR-153-3p 的竞争性内源性 RNA (ceRNA) 来改善 PTEN 的表达。此外，PTEN 的强制表达在调节 MPP+ 处理的 SH-SY5Y 细胞的活力和凋亡方面表现出与 SNHG1 过表达相似的功能。最后，发现 SNHG1 通过靶向 miR-153-3p 激活 SH-SY5Y 细胞中的 PTEN/AKT/mTOR 信号通路。SNHG1 通过海绵化 miR-153-3p 调节 PTEN/AKT/mTOR 信号传导，在 SH-SY5Y 细胞中加重 MPP+ 诱导的细胞毒性，表明 SNHG1 作为 PD 治疗靶点的潜力。