Myocardial Ischamia Reperfusion Injury Injury

HOTAIR[LncRNA]

miR-126[miRNA]

SRSF1[mRNA]

H9c2 cells

Homo sapiens (human)

Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):9046-9054. doi: 10.26355/eurrev_202009_22850.

LncRNA HOTAIR aggravates myocardial ischemia-reperfusion injury by sponging microRNA-126 to upregulate SRSF1.

Dual-luciferase reporter assay;ELISA;Luciferase reporter assay;

OBJECTIVE: Acute myocardial infarction (AMI) is a severe fatal disease throughout the world. Myocardial IR limits the recovery of impaired cardiac function in AMI patients. This study aims to elucidate the role of long non-coding RNA (lncRNA) HOTAIR in myocardial ischemia-reperfusion (IR) and the underlying mechanism, thus providing a novel therapy for AMI. MATERIALS AND METHODS: Myocardial IR model in mice was firstly constructed by LAD. Plasma levels of LDH, CK-MB, HOTAIR, and microRNA-126 in mice were detected. Subsequently, in vitro HR model was constructed in H9c2 cells. Regulatory effects of HOTAIR on proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells were determined. Relative levels of inflammatory factors in in vitro HR model were measured by enzyme-linked immunosorbent assay (ELISA). The regulatory loop HOTAIR/microRNA-126/SRSF1 was finally verified by Dual-Luciferase reporter assay. RESULTS: LDH and CK-MB were significantly released in mice with myocardial IR. HOTAIR was upregulated, while microRNA-126 was downregulated in IR mice and H2O2-induced H9c2 cells. Overexpression of HOTAIR stimulated proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells. Besides, overexpression of microRNA-126 inhibited the release of inflammatory factors in H9c2 cells undergoing HR induction. The regulatory loop HOTAIR/microRNA-126/SRSF1 was identified to influence IR development. CONCLUSIONS: HOTAIR aggravates myocardial IR by competitively binding SRSF1 with microRNA-126.