Research Paper Volume 10, Issue 6 pp 1281—1293

CircSNCA downregulation by pramipexole treatment mediates cell apoptosis and autophagy in Parkinson’s disease by targeting miR-7

Qiuling Sang 1, *, , Xiaoyang Liu 1, *, , Libo Wang 1, , Ling Qi 2, , Wenping Sun 1, , Weiyao Wang 2, , Yajuan Sun 1, , Haina Zhang 3, ,

  • 1 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
  • 2 Department of Pathophysiology, Jilin Medical University, Jilin, Jilin 132013, China
  • 3 Department of Rehabilitation, the Second Hospital of Jilin University, Changchun, Jilin 130041, China
* Equal contribution

received: April 21, 2018 ; accepted: May 30, 2018 ; published: June 28, 2018 ;

https://doi.org/10.18632/aging.101466
How to Cite

Copyright: Sang et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We aimed to explore the mechanism of pramipexole (PPX) actions in the treatment of Parkinson’s disease (PD). Genes related to PD and PPX were screened through bioinformatics retrieval. The PD model was constructed by applying 1-methyl-4-phenylpyridinium (MMP+). The RNA expression levels of circSNCA, SNCA, apoptosis-related genes (BCL2, CASP3, BAX, PTEN and P53) and miR-7 were detected by qRT-PCR. Protein expression was determined by western blot. The interactions between circSNCA-miR-7-SNCA were verified by dual luciferase assay and immunofluorescence localization. Cell viability was determined by MTT assay. SNCA and circSNCA expression levels in PD were downregulated after PPX treatment, consistent with the levels of pro-apoptotic genes. CircSNCA increased SNCA expression by downregulating miR-7 in PD as a competitive endogenous RNA (ceRNA). Lower circSNCA expression was associated with the reduced expression of pro-apoptotic (CASP3, BAX, PTEN and P53) proteins. CircSNCA downregulation could decrease apoptosis and induce autophagy in PD. In conclusion, the downregulation of circSNCA by PPX treatment reduced cell apoptosis and promoted cell autophagy in PD via a mechanism that served as a miR-7 sponge to upregulate SNCA.

Abbreviations

PPX: Pramipexole; PD: Parkinson’s disease; ceRNA: competitive endogenous RNA; LBs: Lewy Bodies; circRNA: Circular RNA; AD: Alzheimer’s Disease; DMEM-H: high-glucose Dulbecco’s-modified eagle medium; FBS: fetal bovine serum; DMSO: dimethyl sulfoxide; RIPA: radio-immunoprecipitation assay; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; PVDF: polyvinylidene fluoride; TBST: Tris Buffered Saline Tween; qRT-PCR: Reverse transcription and quantitative PCR; WT: wild-type; MUT: mutated type; 3’-UTR: 3’-untranslated region.