Department of Neurosurgery, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.
Department of Neurology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.
Bioengineered. 2022 Feb;13(2):4493-4516. doi: 10.1080/21655979.2022.2033409.
Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson's disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models and . Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG's function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.
长链非编码 RNA（lncRNA）被认为是神经退行性疾病的调节剂。在这里，我们研究了 lncRNA miR-17-92a-1 簇宿主基因（MIR17HG）在帕金森病（PD）中的作用。用 6-羟多巴胺（6-OHDA）干预 C57BL/6 小鼠和 SH-SY5Y 细胞，建立 PD 模型和 。采用实时定量逆转录聚合酶链反应（qRT-PCR）比较 MIR17HG 和 miR-153-3p 的表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和 Western blot（WB）评估细胞活力和细胞凋亡。通过酶联免疫吸附试验（ELISA）验证 BV2 中α-突触核蛋白（α-syn，SNCA）的表达。使用商业试剂盒评估活性氧（ROS）生成和乳酸脱氢酶（LDH）和超氧化物歧化酶（SOD）活性。通过生物信息学分析、双荧光素酶报告基因检测、RNA 免疫沉淀（RIP）和 qRT-PCR 证实了 miR-153-3p、MIR17HG 和α-突触核蛋白（SNCA）之间的相互作用。PD 患者、小鼠模型和细胞中 MIR17HG 上调，而 miR-153-3p 下调。抑制 MIR17HG 可减轻 PD 小鼠神经元凋亡、小胶质细胞活化和 SNCA 表达。6-OHDA 处理的 SH-SY5Y 细胞条件培养基增强了小胶质细胞炎症，而抑制 MIR17HG 或过表达 miR-153-3p 可抑制炎症反应。MIR17HG 通过海绵吸附 miR-153-3p 并释放 miR-153-3p 的潜在靶点和 SNCA 的抑制作用，增强其功能。总的来说，MIR17HG 通过靶向 miR-153-3p 并上调 SNCA，促进 PD 中神经元凋亡和小胶质细胞炎症。
