Overexpression of microRNA-183 promotes apoptosis of substantia nigra neurons via the inhibition of OSMR in a mouse model of Parkinson's disease

The present study aimed to investigate the effect of microRNA-183 (miR-183) on substantia nigra neurons by targeting oncostatin M receptor (OSMR) in a mouse model of Parkinson's disease (PD). The positive expression rates of OSMR and the apoptosis of substantia nigra neurons were detected by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, respectively. Substantia nigra neurons in normal and PD mice were cultured in vitro. The association between miR-183 and OSMR was verified using a dual luciferase reporter gene assay. The expression of miR-183 and the phosphoinositide 3-kinase-Akt signaling pathway-associated genes were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell apoptosis was detected by flow cytometry. OSMR is the target gene of miR-183. The number of OSMR-positive cells and the apoptotic rate of substantia nigra neurons were increased in the PD group. Neurons transfected with miR-183 mimic exhibited elevated expression levels of miR-183, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-9 and increased apoptotic rate, and reduced expression levels of OSMR, Akt, phosphorylated (p-)Akt, glycogen synthase kinase-3 (GSK-3), p-GSK-3, Bcl-2, insulin-like growth factor 1 (IGF-1), mammalian target of rapamycin (mTOR) and p-mTOR. The miR-183 inhibitor decreased the expression levels of miR-183, Bax and caspase-9 and the apoptotic rate; however, increased the expression of OSMR, Akt, p-Akt, GSK-3, p-GSK-3, Bcl-2, IGF-1, mTOR and p-mTOR. The results of the present study provide evidence that the overexpression of miR-183 promotes the apoptosis of substantia nigra neurons by inhibiting the expression of OSMR.