Over-expression of microRNA-494 up-regulates hypoxia-inducible factor-1 alpha expression via PI3K/Akt pathway and protects against hypoxia-induced apoptosis

Background: hypoxia-inducible factor-1 alpha (hif-1) is one of the key regulators of hypoxia/ischemia. microrna-494 (mir-494) had cardioprotective effects against ischemia/reperfusion (i/r)-induced injury,but its functional relationship with hif-1 was unknown. this study was undertaken to determine if mir-494 was involved in the induction of hif-1. results: quantitative rt-pcr showed that mir-494 was up-regulated to peak after 4 hours of hypoxia in human liver cell line l02. to investigate the role of mir-494,cells were transfected with mir-494 mimic or mir-negative control,followed by incubation under normoxia or hypoxia. our results indicated that overexpression of mir-494 significantly induced the expression of p-akt,hif-1 and ho-1 determined by qrt-pcr and western blot under normoxia and hypoxia,compared to negative control (p < 0.05). while ly294002 treatment markedly abolished mir-494-inducing akt activation,hif-1 and ho-1 increase under both normoxic and hypoxic conditions (p < 0.05). moreover,apoptosis detection using annexin v indicated that overexpression of mir-494 significantly decreased hypoxia-induced apoptosis in l02 cells,compared to control (p < 0.05). mir-494 overexpression also decreased caspase-3/7 activity by 1.27-fold under hypoxia in l02 cells. conclusions: overexpression of mir-494 upregulated hif-1 expression through activating pi3k/akt pathway under both normoxia and hypoxia,and had protective effects against hypoxia-induced apoptosis in l02 cells. thus,these findings suggested that mir-494 might be a target of therapy for hepatic hypoxia/ischemia injury. © 2013sun et al.; licensee biomed central ltd.