Long non‑coding RNA H19 protects H9c2 cells against hypoxia‑induced injury by activating the PI3K/AKT and ERK/p38 pathways.

Abstract

Myocardial ischemia/reperfusion injury often leads to adverse cardiovascular outcomes due to severe hypoxia. The present study aimed to evaluate the effects and mechanism of long non-coding RNA H19 (H19) on rat H9c2 cells with hypoxia-induced injury. H9c2 cells were infected with lentiviruses to express H19 or H19-targeting short hairpin RNA (shRNA), or their respective controls, at a multiplicity of infection of 1:100. H19 expression was determined by reverse transcription-quantitative PCR. Hypoxic injury was induced and assessed by analyzing the level of apoptosis, the cell cycle distribution and the mitochondrial membrane potential using flow cytometry in the different groups. The expression of the PI3K/AKT and the ERK/p38 signaling pathways were analyzed using western blotting. It was found that hypoxia stimulated apoptosis, induced G1 phase cell cycle arrest and increased the mitochondrial depolarization rate in H9c2 cells. When compared with the hypoxic model group, the H19 overexpression group had a significantly reduced rate of apoptosis (P=0.016), a smaller G1 population and a higher S phase population (P=0.018 and P=0.031, respectively), and a reduced mitochondrial depolarization rate (P=0.036). By contrast, the H19 shRNA group exhibited the opposite trends, suggesting that hypoxia-induced injury was alleviated by the overexpression of H19 and was aggravated by the knockdown of H19. The present mechanistic studies revealed that H19 may decrease hypoxia-induced cell injury by activating the PI3K/AKT and ERK/p38 pathways. The results of the present study suggested that H19 may alleviate hypoxia-induced myocardial cell injury through the activation of the PI3K/AKT and ERK/p38 pathways.