Department of Intervention, Central Hospital of Linyi, No. 17, Health Road, Yishui County, 276400, Linyi City, Shandong Province, China.
Department of Neurology, The Third People's Hospital of Linyi, No. 117, Huaxia Road, Linyi Economic and Technological Development Zone, 276023, Shandong Province, China.
Chem Biol Interact. 2019 Jul 1;307:73-81. doi: 10.1016/j.cbi.2019.04.017. Epub 2019 Apr 18.
Parkinson's disease (PD), the second most prevalent age-related neurodegenerative disease, occurs as a result of the loss of dopaminergic neurons in the substantia nigra. Long non-coding RNA-p21 (lnc-p21) has been demonstrated to be upregulated in PD. However, its role in PD is unknown. Here, the results showed that lnc-p21 was highly expressed in human neuroblastoma SH-SY5Y cells treated with MPP. Knockdown of lnc-p21 attenuated the cytotoxicity and cell apoptosis induced by MPP as shown by enhanced cell viability, decreased LDH release and cell apoptosis rate, accompanying with reduction of caspase-3 activity and Bax expression, and enhancement of Bcl-2 expression. Furthermore, knockdown of lnc-p21 mitigated MPP-induced oxidative stress and neuroinflammation, as evidenced by the decrease in ROS generation, increase in SOD activity and decline in TNF-α, IL-1β and IL-6 levels. Conversely, overexpression of lnc-p21 resulted in the opposite effect. miR-625 was identified as a target of lnc-p21. lnc-p21 overturned the inhibitory effect of miR-625 on MPP-induced neuronal injury in SH-SY5Y cells. Additionally, lnc-p21 positively regulated TRPM2 expression by targeting miR-625, and knockdown of TRPM2 inhibited MPP-induced neuronal injury. Overall, our study identified a new lnc-p21-miR-625-TRPM2 regulatory network that lnc-p21 regulated MPP + -induced neuronal injury by sponging miR-625 and upregulating TRPM2 in SH-SY5Y cells, which provide a better understanding for the pathogenesis of PD.
帕金森病（PD）是第二大常见的与年龄相关的神经退行性疾病，是由于黑质中的多巴胺能神经元丧失引起的。长链非编码 RNA-p21（lnc-p21）已被证明在 PD 中上调。然而，其在 PD 中的作用尚不清楚。在这里，结果表明，lnc-p21 在人神经母细胞瘤 SH-SY5Y 细胞中用 MPP 处理时高度表达。lnc-p21 的敲低减弱了 MPP 诱导的细胞毒性和细胞凋亡，表现为细胞活力增强，LDH 释放和细胞凋亡率降低，伴随着 caspase-3 活性和 Bax 表达降低，以及 Bcl-2 表达增强。此外，lnc-p21 的敲低减轻了 MPP 诱导的氧化应激和神经炎症，表现为 ROS 生成减少，SOD 活性增加，TNF-α、IL-1β 和 IL-6 水平降低。相反，lnc-p21 的过表达则产生相反的效果。miR-625 被鉴定为 lnc-p21 的靶标。lnc-p21 推翻了 miR-625 对 MPP 诱导的 SH-SY5Y 细胞神经元损伤的抑制作用。此外，lnc-p21 通过靶向 miR-625 正向调节 TRPM2 表达，而 TRPM2 的敲低抑制了 MPP 诱导的神经元损伤。总之，我们的研究确定了一个新的 lnc-p21-miR-625-TRPM2 调控网络，lnc-p21 通过海绵吸附 miR-625 和上调 TRPM2 来调节 MPP + 诱导的神经元损伤，这为 PD 的发病机制提供了更好的理解。
