Long non-coding RNA H19 (
lncRNA H19) was found to be upregulated by
hypoxia, its expression and function have never been tested in
cerebral ischemia and reperfusion (I/R) injury. This study intended to investigate the role of
lncRNA H19 and H19 gene variation in cerebral I/R injury with focusing on its relationship with autophagy activation. Cerebral I/R was induced in rats by
middle cerebral artery occlusion followed by reperfusion. SH-SY5Y cells were subjected to
oxygen and
glucose deprivation and reperfusion (OGD/R) to simulate I/R injury. Real-time PCR, flow cytometry, immunofluorescence and Western blot were used to evaluate the level of
lncRNA H19, apoptosis, autophagy and some related
proteins. The modified multiple
ligase reaction was used to analyze the gene polymorphism of six SNPs in H19, rs217727, rs2067051, rs2251375, rs492994, rs2839698 and rs10732516 in
ischemic stroke patients. We found that the expression of
lncRNA H19 was upregulated by cerebral I/R in rats, as well as by OGD/R in vitro in the cells. Inhibition of
lncRNA H19 and autophagy protected cells from OGD/R-induced death, respectively. Autophagy activation induced by OGD/R was prevented by H19
siRNA. Autophagy inducer,
rapamycin, abolished
lncRNA H19 effect. Furthermore, we found that
lncRNA H19 inhibited autophagy through DUSP5-ERK1/2 axis. The result from blood samples of ischemic patients revealed that the variation of H19 gene increased the risk of
ischemic stroke. Taken together, the results of present study suggest that
LncRNA H19 could be a new therapeutic target of
ischemic stroke.