MiR-211 protects cerebral ischemia/reperfusion injury by inhibiting cell apoptosis
Wenyi Liu, Yuanqing Miao, Lin Zhang, Xiaolin Xu, Qi Luan
Abstract
MicroRNAs (miRNAs) have emerged as critical regulators of neuronal survival during cerebral ischemia/reperfusion injury. Accumulating evidence has shown that miR-211 plays a crucial role in regulating apoptosis and survival in various cell types. However, whether miR-211 is involved in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unknown. In this study, we aimed to explore the biological role of miR-211 in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and transient cerebral ischemia/reperfusion (I/R) injury in vitro and in vivo. We found that miR-211 expression was significantly downregulated in PC12 cells in response to OGD/R and in the penumbra of mouse in response to MCAO. Overexpression of miR-211 alleviated OGD/R-induced PC12 cell apoptosis, whereas miR-211 inhibition facilitated OGD/R-induced PC12 cell apoptosis in vitro. Moreover, overexpression of miR-211 reduced infarct volumes, neurologic score, and neuronal apoptosis in vivo, whereas miR-211 inhibition increased infarct volumes, neurologic score and neuronal apoptosis in vivo. Notably, our results identified P53-up-regulated modulator of apoptosis (PUMA) as a target gene of miR-211. Our findings suggested that miR-211 may protect against MCAO injury by targeting PUMA in rats, which paves a potential new way for the therapy of cerebral I/R injury.