Long noncoding RNA myocardial infarction associated transcript promotes the development of thoracic aortic by targeting microRNA-145 via the PI3K/Akt signaling pathway.

Abstract

The main aim of our study was to investigate the roles and molecular basis of long noncoding RNA myocardial infarction associated transcript (MIAT) in the development of thoracic aortic aneurysm. RT-qPCR assay was performed to measure the expressions of MIAT, microRNA-145 (miR-145), along with Bcl-2 and Bcl-xl messenger RNAs. Western blot assay was conducted to determine protein levels of Bcl-2, Bcl-xl, phosphorylated-Akt (p-Akt), and total Akt (t-Akt). Cell viability was detected by the (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The relationship of MIAT and miR-145 was examined by bioinformatics analysis and luciferase reporter assay. MIAT expression was significantly increased, and miR-145 expression was markedly reduced in thoracic aortic aneurysms compared with normal thoracic aortic tissues. MIAT overexpression or miR-145 depletion improved cell viability and inhibited cell apoptosis in human aortic vascular smooth muscle cells (h-VSMCs). Further exploration revealed that MIAT could inhibit miR-145 expression by direct interaction. And miR-145 upregulation abrogated MIAT-induced viability increase and apoptosis inhibition in h-VSMCs. Moreover, MIAT inhibited the activation of Akt signaling, while this effect was abated by miR-145 overexpression in h-VSMCs. The inhibition of the Akt pathway by MK-22062HCl resulted in the reduction of cell viability and the increase of cell apoptotic activity in h-VSMCs. Akt activation by HY-18749 improved cell viability and suppressed cell apoptosis in h-VSMCs. And the introduction of HY-18749 raised cell viability and curbed cell apoptosis in h-VSMCs cotransfected with MIAT overexpression plasmid and miR-145 mimic. lncRNA-MIAT could target miR-145 to affect the viability and apoptosis of h-VSMCs, which was implicated in the regulation of the PI3K/Akt signaling pathway.