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微小RNA-205通过甲基化修饰调控帕金森病中多巴胺能神经元的表达

MiR-205 Regulates Expression in Dopamine Neurons in Parkinson's Disease through Methylation Modification.

作者信息

Wang Hongwei, Li Jie, Tao Liang, Lv Luting, Sun Jinghui, Zhang Tengteng, Wang Huimin, Wang Jiandong

机构信息

Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China.

Department of Cardiology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China.

出版信息

Iran J Public Health. 2022 Jul;51(7):1637-1647. doi: 10.18502/ijph.v51i7.10098.

Abstract

BACKGROUND

We explored the methylation modification in miR-205 promoter during the pathological changes of Parkinson's disease (PD) and its regulation on (, clarified the important role of methylation in miR-205 promoter region in PD, explained the role of miR-205 methylation in the pathological changes of PD, and looked for new targets for PD.

METHODS

Methylation of miR-205 promoter regions was determined by cell genomic DNA, with model bisulfite treatment, and the transcription of miR-205 and in PD model cells was determined by qPCR, and expression was determined by Western blot. The binding sites of miRNAs in the non-coding region of were analyzed by the targetscan database, and miR-205 expression in 293T cells was controlled. The correlation between miR-205 expression and was determined to clarify the regulation mode of miR-205 on .

RESULTS

The level of miR-205 were reduced in the SH-SY5Y Parkinson model cells, and its promoter region was highly methylated, while expression decreased in the model cells after 5-Azacytidine inhibition of methylation in miR-205 promoter region. According to the target scan database analysis, non-coding region is a miR-205-specific binding site. After further miR-205 overexpression in 293T cells, the transcription and translation of decreased in cells, which increased after the treatment of miR-205 inhibitor on .

CONCLUSION

The methylation modification of miR-205 promoter region could regulate the transcription and translation of in dopaminergic neurons, so miR-205 methylation regulation can serve as a new potential target for the treatment of PD.

摘要

背景

我们探讨了帕金森病(PD)病理变化过程中miR-205启动子的甲基化修饰及其调控作用,阐明了甲基化在PD中miR-205启动子区域的重要作用,解释了miR-205甲基化在PD病理变化中的作用,并寻找PD的新靶点。

方法

采用细胞基因组DNA,经亚硫酸氢盐处理后测定miR-205启动子区域的甲基化,通过qPCR测定PD模型细胞中miR-205的转录水平,采用蛋白质免疫印迹法测定其表达。通过targetscan数据库分析其非编码区中miRNAs的结合位点,并调控293T细胞中miR-205的表达。确定miR-205表达与之间的相关性,以阐明miR-205对的调控模式。

结果

SH-SY5Y帕金森模型细胞中miR-205水平降低,其启动子区域高度甲基化,而在5-氮杂胞苷抑制miR-205启动子区域甲基化后,模型细胞中的表达下降。根据targetscan数据库分析,其非编码区是miR-205特异性结合位点。在293T细胞中进一步过表达miR-205后,细胞中的转录和翻译减少,在对进行miR-205抑制剂处理后增加。

结论

miR-205启动子区域的甲基化修饰可调控多巴胺能神经元中的转录和翻译,因此miR-205甲基化调控可作为治疗PD的新潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ab/9529724/4d284ee0b132/IJPH-51-1637-g001.jpg

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