Long non-coding RNA-p21 regulates MPP+-induced neuronal injury by targeting miR-625 and derepressing TRPM2 in SH-SY5Y cells.

Parkinson's disease (PD), the second most prevalent age-related neurodegenerative disease, occurs as a result of the loss of dopaminergic neurons in the substantia nigra. Long non-coding RNA-p21 (lnc-p21) has been demonstrated to be upregulated in PD. However, its role in PD is unknown. Here, the results showed that lnc-p21 was highly expressed in human neuroblastoma SH-SY5Y cells treated with MPP+. Knockdown of lnc-p21 attenuated the cytotoxicity and cell apoptosis induced by MPP+ as shown by enhanced cell viability, decreased LDH release and cell apoptosis rate, accompanying with reduction of caspase-3 activity and Bax expression, and enhancement of Bcl-2 expression. Furthermore, knockdown of lnc-p21 mitigated MPP+-induced oxidative stress and neuroinflammation, as evidenced by the decrease in ROS generation, increase in SOD activity and decline in TNF-α, IL-1β and IL-6 levels. Conversely, overexpression of lnc-p21 resulted in the opposite effect. miR-625 was identified as a target of lnc-p21. lnc-p21 overturned the inhibitory effect of miR-625 on MPP+-induced neuronal injury in SH-SY5Y cells. Additionally, lnc-p21 positively regulated TRPM2 expression by targeting miR-625, and knockdown of TRPM2 inhibited MPP+-induced neuronal injury. Overall, our study identified a new lnc-p21-miR-625-TRPM2 regulatory network that lnc-p21 regulated MPP + -induced neuronal injury by sponging miR-625 and upregulating TRPM2 in SH-SY5Y cells, which provide a better understanding for the pathogenesis of PD.