MiR-181b regulates autophagy in a model of Parkinson's disease by targeting the PTEN/Akt/mTOR signaling pathway.

OBJECTIVE: Parkinson's disease (PD) is the second most common neurodegenerative disease. Recent studies have shown that dysregulation of microRNA plays an important role in PD, and defects in autophagy are also critically associated with mechanisms underlying PD. We aim to investigate the effect of miR-181b on autophagy, particularly the involvement of miR-181b in the regulation of the phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and neuronal autophagy in a 1-methyl-4- phenylpyridinium iodide(MPP+ )-induced cellular model of Parkinson's disease.

MATERIALS AND METHODS: We used MPP+ as a tool to construct the PD cell model, using miR-181b mimics or inhibitors to regulate the expression of miR-181b. PC12 cell viability was detected by MTT. The expression of miR-181b was determined by quantitative real-time PCR analysis. The expression of autophagy protein markers (LC3II) and PTEN/Akt/mTOR signaling proteins (PTEN, p-AKT,p-mTOR and p-p70S6K) were determined by Western blotting analysis.

RESULTS: The expression of miR-181b and autophagy-related proteins was gradually decreased with increasing MPP+ content. Overexpression of miR-181b significantly decreased the LC3II/GAPDH ratio and increased cell viability compared to the MPP+ treated group, whereas inhibition of miR-181b attenuated these effects. In addition, we observed that PTEN expression was reduced by miR-181b mimics and induced by its inhibitors in MPP+ -treated PC12 cells. Additionally, the indicators of AKT/mTOR signaling, phosphorylated (active) AKT, mTOR and p70S6K were both increased by miR-181b mimics and decreased by its inhibitors.

CONCLUSIONS: Our results suggest that miR-181b regulates autophagy by targeting the PTEN/Akt/mTOR signaling pathway, thereby affecting cell viability in PD.