miRNA-1976 regulates apoptosis of dopaminergic neuron cells by targeting to PINK1

Background: Parkinson’s disease (PD) is a degenerative disease, the biomarkers are urgently required to assist with early diagnosis. Objectives We screened for differences in the expression of miRNAs and identified the miR-1976 as a possible biomarker of PD. Methods Twenty-three patients with PD and 30 controls were included in this case-controlled study. The dopamine neuron cells (MES23.5 cells) and the C57BL mice were cultured. The miRNA expression profiles were analyzed using the µParaflo® miRNA microarray. By miRNA microarray assay, miR-1976 was identified as a miRNA that was expressed differently between PD and controls. Lentiviral vectors were constructed for miR-1976, then the effect of apoptosis in dopaminergic neuron cell were analyzed by MTS and flow cytometry. We then used the biological analysis to predict the target gene of miR-1976 and predict its biological effect on MES23.5 cells by transaction of miR-1976 mimics. Results Overexpression of miR-1976 increased the cell apoptosis and mitochondria damage of dopaminergic neuron cells. The bioinformatic analysis showed that the PINK1 was the most common target protein of miR-1976 in MES23.5 cells, and the results were verified by Dual-Luciferase assay. Further analysis demonstrated that silence of PINK1 increased apoptosis of MES23.5 cells and damage of mitochondria. Conclusion miR-1976 is a newly discovered miRNA that exhibits a high degree of differential expression with respect to the apoptosis of dopaminergic neuron cells and, hence, may prove to be a new biomarker for PD. Besides, high expression of miR-1976 might improve PD development by targeting to PINK1.