Protective effects of lncRNA H19 silence against hypoxia-induced injury in PC-12 cells by regulating miR-28

Abstract

LncRNA H19 has been widely reported to be up-regulated upon hypoxia. We aimed to uncover the function and mechanism of lncRNA H19 in hypoxic PC-12 cells. Neural-like PC-12 cells were exposed to hypoxia to stimulating an in vitro model of hypoxic brain damage. The expression levels of lncRNA H19 in PC-12 cells were altered by transfection, then cell viability, migration and apoptosis were assessed respectively. Moreover, the cross-regulation between lncRNA H19, miR-28 and SP1 was studied to reveal one of the possible mechanisms of lncRNA H19's function. We found that hypoxia induced remarkable decreases in cell viability and migration, and induced a notable increase in cell apoptosis. Hypoxia-induced cell damage was aggravated by lncRNA H19 overexpression, while was alleviated by lncRNA H19 silence. miR-28 was negatively regulated by lncRNA H19, and SP1 was a target gene of miR-28. Furthermore, lncRNA H19 down-regulated miR-28 expression, which in turn preventing SP1 from degradation by miR-28, and ultimately deactivated PDK/AKT and JAK/STAT signaling pathways. In conclusion, our research demonstrated a protective role of lncRNA H19 silence in hypoxic PC-12 cells. A possible mechanism of which lncRNA H19 functioned to PC-12 cells was that lncRNA H19 down-regulated miR-28 expression, preventing SP1 exhausted by miR-28.