蛋白激酶B
PI3K/AKT/mTOR通路
心肌梗塞
小RNA
缺血
医学
P70-S6激酶1
免疫印迹
细胞凋亡
缺氧(环境)
生物
内科学
基因
化学
遗传学
有机化学
氧气
标识
DOI:10.1016/j.bbrc.2022.10.101
摘要
Myocardial infarction is a fatal disease that causes millions of deaths worldwide every year. The damage and recovery of cardiomyocytes are closely related to changes in gene expression. miRNA may be a new therapeutic target of myocardial ischemia-reperfusion.The differential expression genes were analyzed based on GSE83500, GSE60993 and GSE154733. miRNA expression profile data and clinical data were downloaded from GSE76591. Bioinformatics analysis including limma package, cluster analysis, WGCNA analysis were performed. H9c2 cell hypoxia model and mouse myocardial ischemia model were established. Q-PCR, Western blot and luciferase assay were carried out.miR-1322 was identified as a significantly differentially expressed miRNA in myocardial ischemi. Yin Yang 1(YY1) was significantly highly expressed in cells with hypoxia treatment (P < 0.05), and myocardial ischemia mice (P < 0.01), which was identified as the transcription factor of miR-1322. The protein expression of LRP8 was lower in cells with hypoxia treatment and myocardial ischemia mice (P < 0.05) and LRP8 was the target gene of miR-1322. The overexpression of LRP8 could significantly increase the expression of p-PI3K, p-AKT, and P70 S6K (P < 0.05). LRP8 regulated PI3K/AKT/P70 S6K signaling pathway, eventually resulting in cell apoptosis.Our results suggested that miR-1322 can protect against the myocardial ischemia via LRP8/PI3K/AKT pathway.
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