Zheng Yanhua, Liu Junpeng, Zhuang Jiajun, Dong Xiaoyan, Yu Miao, Li Zhihui
Department of Neurology, Weifang People's Hospital, Weifang, 261041, Shandong, China.
Department of Neurology, Weifang Brain Hospital, No. 553, Dongfeng West Street, Weicheng District, Weifang, 261021, Shandong, China.
Neurochem Res. 2021 Apr;46(4):878-887. doi: 10.1007/s11064-020-03214-9. Epub 2021 Jan 19.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been implicated in PD development. Nevertheless, little insight has been gained on the mechanisms of UCA1 in PD pathogenesis. The levels of UCA1, miR-423-5p and potassium channel tetramerization domain containing 20 (KCTD20) were assessed by qRT-PCR and western blot. Cell viability was gauged by the CCK-8 assay, and cell apoptosis was detected by flow cytometry. Targeted relationships among UCA1, miR-423-5p and KCTD20 were verified by dual-luciferase reporter and RNA immunoprecipitation assays. Our data showed that MPP induced UCA1 expression in SK-N-SH cells. UCA1 silencing protected against MPP-evoked cytotoxicity in SK-N-SH cells. UCA1 functioned as a miR-423-5p sponge, and the protective impact of UCA1 silencing on MPP-evoked cytotoxicity was mediated by miR-423-5p. KCTD20 was a direct target of miR-423-5p, and miR-423-5p overexpression mitigated MPP-triggered cell injury by down-regulating KCTD20. Furthermore, UCA1 regulated KCTD20 expression by acting as a sponge of miR-423-5p in SK-N-SH cells. Our study first identified that the silencing of UCA1 protected SK-N-SH cells from MPP-evoked cytotoxicity at least in part by targeting the miR-423-5p/KCTD20 axis.
帕金森病（PD）是第二常见的神经退行性疾病。长链非编码RNA（lncRNA）尿路上皮癌相关1（UCA1）与PD的发生发展有关。然而，关于UCA1在PD发病机制中的作用机制，我们了解甚少。通过qRT-PCR和蛋白质免疫印迹法评估UCA1、miR-423-5p和含钾通道四聚化结构域20（KCTD20）的水平。通过CCK-8法检测细胞活力，通过流式细胞术检测细胞凋亡。通过双荧光素酶报告基因和RNA免疫沉淀试验验证UCA1、miR-423-5p和KCTD20之间的靶向关系。我们的数据表明，MPP诱导SK-N-SH细胞中UCA1的表达。UCA1沉默可保护SK-N-SH细胞免受MPP诱导的细胞毒性。UCA1作为miR-423-5p的海绵发挥作用，UCA1沉默对MPP诱导的细胞毒性的保护作用是由miR-423-5p介导的。KCTD20是miR-423-5p的直接靶点，miR-423-5p过表达通过下调KCTD20减轻MPP触发的细胞损伤。此外，在SK-N-SH细胞中，UCA1通过作为miR-423-5p的海绵来调节KCTD20的表达。我们的研究首次发现，UCA1沉默至少部分通过靶向miR-423-5p/KCTD20轴保护SK-N-SH细胞免受MPP诱导的细胞毒性。
