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

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

doi:10.18502/ijph.v51i7.10098

Hongwei Wang Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Jie Li Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Liang Tao Department of Cardiology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Luting Lv Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Jinghui Sun Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Tengteng Zhang Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Huimin Wang Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China
Jiandong Wang Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161006, China

DOI: https://doi.org/10.18502/ijph.v51i7.10098

Keywords: Parkinson's disease; miR-205; RNA interference

Abstract

Background: We explored the methylation modification in miR-205 promoter during the pathological changes of Parkinson's disease (PD) and its regulation on Leucine-Rich Repeat Kinase 2 (LRRK2), 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 LRRK2 in PD model cells was determined by qPCR, and LRRK2 expression was determined by Western blot. The binding sites of miRNAs in the non-coding region of LRRK2 were analyzed by the targetscan database, and miR-205 expression in 293T cells was controlled. The correlation between miR-205 expression and LRRK2 was determined to clarify the regulation mode of miR-205 on LRRK2.

Results: The level of miR-205 were reduced in the SH-SY5Y Parkinson model cells, and its promoter region was highly methylated, while LRRK2 expression decreased in the model cells after 5-Azacytidine inhibition of methylation in miR-205 promoter region. According to the target scan database analysis, LRRK2 non-coding region is a miR-205-specific binding site. After further miR-205 overexpression in 293T cells, the transcription and translation of LRRK2 decreased in cells, which increased after the treatment of miR-205 inhibitor on LRRK2.

Conclusion: The methylation modification of miR-205 promoter region could regulate the transcription and translation of LRRK2 in dopaminergic neurons, so miR-205 methylation regulation can serve as a new potential target for the treatment of PD.