Modulation in miR-200a/SIRT1axis is associated with apoptosis in MPP-induced SH-SY5Y cells.

Previous studies have shown that miR-200a is markedly deregulated in various neurodegenerative disorders including Alzheimer's disease (AD), Multiple Sclerosis (MS) and PD. Furthermore, studies have shown the key role of miR-200a on expression of SIRT1 and apoptosis. Therefore, we hypothesized that miR-200a/SIRT1 axis should have a crucial role in apoptosis of dopaminergic (DA)neurons. In this study, human SH-SY5Y cells were treated with MPP+ and expression of miR-200a, SIRT1 and its target genes were assessed. Our results confirmed that expression of miR-200a significantly up-regulated during treating of human SH-SY5Y cells with MPP in order to induce oxidative stress and apoptosis. Additionally, transcript level of SIRT1 in these cells showed significant down-regulation confirming that SIRT1 is indeed decreased due to miR-200a up-regulation during apoptosis. Moreover, expression of P53, FOXO1 and BCL2 were modulated. In this study, we indicated that miR-200a/SIRT1 axis directly correlates with apoptosis and P53 signaling pathway. In conclusion, miR-200a and its target gene, SIRT1, may exert a possible role in induction of apoptosis in DA neurons through regulating P53, apoptosis and FOXO signaling pathways.