MicroRNA-205通过甲基化修饰调节帕金森病多巴胺神经元LRRK2表达  

MicroRNA-205 Regulates LRRK2 Expression in Dopamine Neurons of Parkinson's Disease through Methylation Modification

作　　者：王洪伟[1] 陶亮 吕禄廷 孙静慧 张腾腾 李杰[1] 王建东[1] WANG Hongwei;TAO Liang;LYU Luting;SUN Jinghui;ZHANG Tengteng;LI Jie;WANG Jiandong(Department of Neurology,the Second Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang Province,161006 China;Department of Cardiology,the Second Affiliated Hospital of Qiqihar Medical College,Qiqihar,Heilongjiang Province,161006 China)

机构地区：[1]齐齐哈尔医学院附属第二医院神经内科,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院附属第二医院心内科,黑龙江齐齐哈尔161006

出　　处：《系统医学》2023年第7期16-20,共5页Systems Medicine

基　　金：齐齐哈尔医学科学院项目(QMSI2021M-20)。

摘　　要：目的探讨MicroRNA-205(miR-205)如何调节LRRK2表达从而在帕金森病中发挥作用。方法诱导人神经母细胞瘤细胞(SH-SY5Y)成为PD细胞模型,检测PD细胞模型中miR-205以及LRRK2的表达量;转染前体miR-205,使miR-205过表达,随后q-PCR方法检测miR-205过表达PD模型细胞中LRRK2转录水平变化;转染miR-205抑制剂,随后q-PCR方法检测miR-205抑制PD模型细胞中LRRK2转录水平变化。结果相较于正常细胞(1.02±0.14),PD模型细胞中miR-205的表达水平明显降低(0.59±0.03),差异有统计学意义(P=0.017);而相较于正常细胞(1.00±0.11),PD模型细胞中LRRK2水平上调(1.50±0.10),差异有统计学意义(P=0.033);相较于正常细胞(1.02±0.11)以及PD模型细胞(1.47±0.12),使用前体miR-205处理SH-SY5Y细胞可持续抑制LRRK2蛋白表达约50%(0.87±0.11),差异有统计学意义(P=0.020);相较于正常细胞(1.02±0.11)以及PD模型细胞(1.47±0.12),转染miR-205抑制剂后可诱导神经元培养物中LRRK2蛋白表达的剂量依赖性上调(1.87±0.11),差异有统计学意义(P=0.036)。结论miR-205可抑制LRRK2的转录水平。过表达miR-205可能成为LRRK2-PD的治疗手段。Objective To explore how microRNA-205(miR-205)regulates LRRK2 expression and thus plays a role in Parkinson's disease.Methods Human neuroblastoma cells(SH-SY5Y)were induced to become a PD cell model,and the expression of miR-205 and LRRK2 in the PD cell model was detected.The precursor miR-205 was transfected to make miR-205 overexpressed.Subsequently q-PCR method was used to detect changes in LRRK2 transcript levels in miR-205 overexpression PD model cells.Transfection of miR-205 inhibitor,followed by q-PCR method to detect changes in LRRK2 transcript levels in miR-205 inhibited PD model cells.Results The expression level of miR-205 was significantly decreased in PD model cells(0.59±0.03)compared to normal cells(1.02±0.14),the difference was statistically significant(P=0.017);while the level of LRRK2 was upregulated in PD model cells(1.50±0.10)compared to normal cells(1.00±0.11),the difference was statistically significant(P=0.033);compared to normal cells(1.02±0.11)as well as PD model cells(1.47±0.12),treatment of SH-SY5Y cells with the precursor miR-205 consistently inhibited LRRK2 protein expression by approximately 50%(0.87±0.11),the difference was statistically significant(P=0.020);transfection with miR-205 inhibitor induced a dose-dependent upregulation of LRRK2 protein expression in neuronal cultures(1.87±0.11)compared to normal cells(1.02±0.11)as well as PD model cells(1.47±0.12),the difference was statistically significant(P=0.036).Conclusion miR-205 suppresses the transcriptional level of LRRK2.Overexpression of miR-205 may be a therapeutic tool for LRRK2-PD.

关 键 词：MicroRNA-205 帕金森病 LRRK2 

分 类 号：R3[医药卫生—基础医学]