Noncoding RNAs including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been documented to play prominent role in neurodegenerative diseases including Parkinson’s disease (PD). This study intended to investigate the role of lncRNA nuclear enriched assembly transcript 1 (NEAT1) in MPP⁺-induced PD model in dopaminergic neuronblastoma SK-N-SH cells, as well as its mechanism through sponging miRNA (miR)-1277-5p. Real-time PCR and western blotting revealed that NEAT1 and ARHGAP26 were upregulated, and miR-1277-5p was downregulated in MPP⁺-treated SK-N-SH cells in a certain of concentration- and time- dependent manner. MPP⁺ induced apoptosis in SK-N-SH cells, as evidenced by decreased cell viability and Bcl-2 expression, and elevated apoptosis rate and levels of Bax and cleaved caspase-3, which were examined by MTT assay, flow cytometry and western blotting. Moreover, commercial assay kits indicated that inflammatory response and oxidative stress were provoked in response to MPP⁺, due to promoted contents of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, malondialdehyde, and lactate dehydrogenase, accompanied with suppressed superoxide dismutase and glutathione peroxidase levels. Notably, MPP⁺-induced apoptosis, inflammatory response and oxidative stress in SK-N-SH cells were mitigated by NEAT1 knockdown and/or miR-1277-5p overexpression. Moreover, silencing of miR-1277-5p could abrogate the suppression of NEAT1 deficiency on MPP⁺-induced cell injury. Similarly, upregulating miR-1277-5p-elicited neuroprotection in MPP⁺-induced SK-N-SH cells was reversed by ARHGAP26 restoration. Dual-luciferase reporter assay demonstrated a direct interaction between miR-1277-5p and NEAT1 or ARHGAP26. Collectively, NEAT1 upregulation might contribute to MPP⁺-induced neuron injury via NEAT1-miR-1277-5p-ARHGAP26 competing endogenous RNAs (ceRNAs) pathway.

包括长非编码 RNA (lncRNA) 和微 RNA (miRNA) 在内的非编码 RNA 已被证明在包括帕金森病 (PD) 在内的神经退行性疾病中发挥重要作用。本研究旨在研究lncRNA核富集组装转录物1（NEAT1）在MPP ⁺诱导的多巴胺能神经母细胞瘤SK-N-SH细胞PD模型中的作用，及其通过海绵miRNA（miR）-1277-5p的机制。实时 PCR 和蛋白质印迹显示 NEAT1 和 ARHGAP26 上调，而 miR-1277-5p 在 MPP ⁺处理的 SK-N-SH 细胞中以一定的浓度和时间依赖性方式下调。MPP ⁺诱导 SK-N-SH 细胞凋亡，这表现为细胞活力和 Bcl-2 表达降低，以及凋亡率和 Bax 和裂解的 caspase-3 水平升高，这通过 MTT 测定、流式细胞术和蛋白质印迹进行了检查。此外，商业检测试剂盒表明，由于白细胞介素 (IL)-6、IL-1β、肿瘤坏死因子-α、丙二醛和乳酸脱氢酶的含量增加，MPP ^{+ 会}引发炎症反应和氧化应激，并伴有抑制超氧化物歧化酶和谷胱甘肽过氧化物酶水平。值得注意的是，MPP ⁺NEAT1 敲低和/或 miR-1277-5p 过表达可减轻 SK-N-SH 细胞中诱导的细胞凋亡、炎症反应和氧化应激。此外，miR-1277-5p 的沉默可以消除 NEAT1 缺陷对 MPP ⁺诱导的细胞损伤的抑制。类似地，在 MPP ⁺诱导的 SK-N-SH 细胞中上调 miR-1277-5p 引发的神经保护作用被 ARHGAP26 修复逆转。双荧光素酶报告基因检测表明 miR-1277-5p 与 NEAT1 或 ARHGAP26 之间存在直接相互作用。总的来说，NEAT1 上调可能通过 NEAT1-miR-1277-5p-ARHGAP26 竞争性内源 RNA (ceRNAs) 途径导致 MPP ⁺诱导的神经元损伤。