Yuan Dahua, Wang Qun, Ding Nan, Du Pu, Peng Lingmei, Duan Zhenpeng, Pan Suyue
Department of Neurology, Nanfang Hospital, Southern Medical University 1023-1063, Sha Tai Road, Baiyun District 510515 Guangzhou China
Department of Neurology, The First People's Hospital of Foshan Foshan China.
RSC Adv. 2019 Jan 4;9(2):690-698. doi: 10.1039/c8ra09260e. eCollection 2019 Jan 2.
Parkinson's disease (PD) is the most common neurodegenerative disease and its incidence is rising. Long noncoding RNAs (lncRNAs) have been reported to have essential roles in development of PD. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is dysregulated in PD, while the role of MALAT1 and its mechanism in PD remain poorly understood. In this study, SH-SY5Y cells were exposed to 1-methyl-4-phenylpyridinium (MPP) to induce a PD model . Then we explored the effect of MALAT1 on cell viability, apoptosis and inflammatory response as well as its interaction with miR-212 in MPP-treated SH-SY5Y cells. The results showed that MALAT1 was up-regulated in MPP-treated SH-SY5Y cells compared with that in the normal group. Overexpression of MALAT1 exacerbated MPP-induced neuronal injury, uncovered by inhibition of cell viability and increase of cell apoptosis as well as inflammatory cytokine expressions in SH-SY5Y cells. However, knockdown of MALAT1 exerted the opposite effect in MPP-treated SH-SY5Y cells. Moreover, MALAT1 was bound to miR-212 and negatively regulated the miR-212 level. Furthermore, addition of miR-212 ablated the regulatory effect of MALAT1 on MPP-induced neuronal injury, as indicated by restoration of cell viability and lower apoptotic rate along with inflammatory cytokine levels in SH-SY5Y cells. Therefore, we concluded that MALAT1 exacerbated MPP-induced neuronal injury through regulating cell viability, apoptosis and inflammatory cytokines by sponging miR-212, providing a novel theoretical foundation for application of MALAT1 in PD.
帕金森病（PD）是最常见的神经退行性疾病，其发病率正在上升。据报道，长链非编码RNA（lncRNAs）在PD的发展中起重要作用。lncRNA转移相关肺腺癌转录本1（MALAT1）在PD中表达失调，而MALAT1在PD中的作用及其机制仍知之甚少。在本研究中，将SH-SY5Y细胞暴露于1-甲基-4-苯基吡啶鎓（MPP）以诱导PD模型。然后我们探讨了MALAT1对MPP处理的SH-SY5Y细胞的细胞活力、凋亡和炎症反应的影响，以及它与miR-212的相互作用。结果表明，与正常组相比，MPP处理的SH-SY5Y细胞中MALAT1上调。MALAT1的过表达加剧了MPP诱导的神经元损伤，表现为SH-SY5Y细胞活力的抑制、细胞凋亡的增加以及炎症细胞因子表达的增加。然而，敲低MALAT1在MPP处理的SH-SY5Y细胞中产生相反的效果。此外，MALAT1与miR-212结合并负调节miR-212水平。此外，添加miR-212消除了MALAT1对MPP诱导的神经元损伤的调节作用，表现为SH-SY5Y细胞活力的恢复、较低的凋亡率以及炎症细胞因子水平的降低。因此，我们得出结论，MALAT1通过海绵化miR-212调节细胞活力、凋亡和炎症细胞因子，从而加剧MPP诱导的神经元损伤，为MALAT1在PD中的应用提供了新的理论基础。
