LncRNA DLX6-AS1 promotes necroptosis through PI3K/AKT/mTOR signaling pathway in myocardial ischemia/reperfusion injury mice

Abstract

Myocardial ischemia/reperfusion injury (MIRI) leads to life-threatening myocardial infarction. Necroptosis is involved in MIRI. The lncRNA DLX6-AS1 was found to participate in the context of MIRI. In this article, we examined the effect of DLX6-AS1 on ischemia perfusion-induced myocardial injury caused by necroptosis and the underlying potential mechanism. We constructed a mouse model of MIRI, and hematoxylin-eosin staining, TUNEL staining, echocardiology, Western blotting (WB), and reverse transcriptase-polymerase chain reaction (RT‒PCR) were employed to evaluate myocardial infarction and necroptosis. Rat H9c2 cells were induced by hypoxia-reoxygenation (H/R), and we analyzed the possible mechanism by overexpressing and inhibiting DLX6-AS1 expression. Cell Counting Kit 8, lactate dehydrogenase (LDH), flow cytometry, RT‒PCR, and WB were utilized to examine cell injury, apoptosis, and relative protein expression. MIRI induced myocardial damage and impaired cardiac function in mice. Ischemia/reperfusion injury results in necroptosis, a process that Nec-1 inhibits. The mRNA levels of RIP1, RIP3, and MLKL were increased, and DLX6-AS1 demonstrated an increase in the IR model, indicating that DLX6-AS1 was associated with necroptosis. Furthermore, H/R-induced H9C2 cells exhibited high LDH levels, low cell activity, and severe apoptosis levels. DLX6-AS1 overexpression caused cell damage and necroptosis and increased the expression of proteins, including PI3K, p-PI3K, AKT, p-AKT, mTOR and p-mTOR. DLX6-AS1 inhibition suppressed necroptosis and cell damage through the PI3K/AKT/mTOR signaling pathway. Myocardial ischemia‒reperfusion injury induces necroptosis, and DLX6-AS1 promotes this process through the PI3K/AKT/mTOR signaling pathway.