Long non-coding RNA MALAT1 modulates myocardial ischemia-reperfusion injury though the PI3K/Akt/eNOS pathway by sponging miRNA-133a-3p to target IGF1R expression

This study aimed to elucidate the roles and possible mechanism of MALAT1 in myocardial IR injury. IR model was established in rats by ligation of the anterior descending artery in vivo, and H9c2 and HL-1 cells were treated by hypoxia/reoxygenation (HR) to construct the model in vitro. The small interfering RNA (siRNA) for MALAT1 and miR-133a-3p mimics, inhibitor was used to transfect the cells. The expression of MALAT1, miR-133a-3p in MIRI were evaluated using real-time quantitative polymerase chain reaction (qRT-PCR)，immunohistochemistry (IHC) and western blot (WB). Relationships between MALAT1, insulin-like growth factor 1 receptor (IGF1R) with miR-133a-3p were confirmed by luciferase reporter assay. Annexin V-FITC/PI double-labeled flow cytometry, terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Cell Counting Kit-8 (CCK-8), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were evaluated to examine the impact of MALAT1 on MIRI. Our results revealed that MALAT1 was highly expressed, while miR-133a-3p and IGF1R were repressed in IR and HR groups. Knockdown of MALAT1 alleviate the pro-apoptotic effect and myocardial injury in vitro and in vivo. Systematically, MALAT1 may serve as a sponge for miR-133a-3p to suppress IGF1R, which a direct target of miR-133a-3p, then inhibit the PI3K/Akt/eNOS survival pathway. Mechanistically, our study demonstrated that MALAT1 regulates PI3K/Akt/eNOS signaling via miR-133a-3p. In summary, these re...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research