Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease.
Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease.
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DOI：
10.1186/s13578-017-0147-5
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发表时间：
2017
影响因子：
7.5
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Liu W;Zhang Q;Zhang J;Pan W;Zhao J;Xu Y
帕金森病（Parkinson disease，PD）是一种以中脑多巴胺能（dopaminergic，DA）神经元缺失为主要特征的运动障碍性疾病。转移相关肺腺癌转录本1（MALAT 1）在神经元中异常表达，并参与树突和突触发育。然而，MALAT 1在PD中的作用及其潜在机制仍有待确定。通过qRT-PCR评估MALAT 1和miR-124的表达。采用N-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的PD小鼠模型和经N-甲基-4-苯基吡啶（MPP+）处理的SH-SY 5 Y细胞，研究MALAT 1对PD的影响。TUNEL法检测PD小鼠DA能神经元凋亡情况。流式细胞仪检测SH-SY 5 Y细胞凋亡情况。Caspase 3活性检测试剂盒检测Caspase 3活性，Western blot检测Cleaved Caspase 3表达。利用TargetScan软件和荧光素酶报告基因分析方法探讨MALAT 1与miR-124之间的关系。MPTP诱导的PD小鼠和MPP+处理的SH-SY 5 Y细胞中MALAT 1上调，miR-124下调。在MPTP诱导的PD小鼠模型中，MALAT 1敲低减弱了MPTP诱导的DA神经元凋亡。MALAT 1与miR-124相互作用，负调控其表达。MALAT 1敲低抑制MPP+诱导的SH-SY 5 Y细胞凋亡，而miR-124下调消除了这种作用。此外，MALAT 1敲低改善了MPTP/MPP+诱导的PD模型中的miR-124表达。MALAT 1在PD小鼠模型和PD体外模型中均通过海绵状作用促进miR-124的凋亡，为MALAT 1抗PD的临床应用提供了潜在的理论基础。
Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined. The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP+) were utilized to investigate the effect of MALAT1 on PD. TUNEL assay was performed to detect apoptosis of DA neurons in PD mice. Flow cytometry analysis was carried out to measure apoptosis of SH-SY5Y cells. Caspase3 activity and Cleaved Caspase3 expression were tested by caspase3 assay kit and western blot, respectively. TargetScan software and luciferase reporter assay were used to explore the relationship between MALAT1 and miR-124. MALAT1 was up-regulated and miR-124 was down-regulated in MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. MALAT1 knockdown attenuated MPTP-induced apoptosis of DA neurons in MPTP-induced PD mouse model. MALAT1 interacted with miR-124 to negatively regulate its expression. MALAT1 knockdown suppressed MPP+-induced apoptosis in SH-SY5Y cells, while miR-124 downregulation abrogated this effect. Moreover, MALAT1 knockdown improved miR-124 expression in MPTP/MPP+ induced models of PD. MALAT1 promotes the apoptosis by sponging miR-124 in mouse models of PD and in vitro model of PD, providing a potential theoretical foundation for the clinical application of MALAT1 against PD.