Long non-coding RNA MIAT regulates ox-LDL-induced cell proliferation, migration and invasion by miR-641/STIM1 axis in human vascular smooth muscle cells

Abstract

Background Atherosclerosis (AS) is a primary cause of coronary heart and vascular diseases. Long non-coding RNAs (lncRNAs) are indicated to regulate AS progression. This study aimed to reveal the biological roles of lncRNA myocardial infarction associated transcript (MIAT) in oxidized low-density lipoprotein (ox-LDL)-induced human vascular smooth muscle cells (VSMCs). Methods The RNA levels of MIAT, microRNA-641 (miR-641) and stromal interaction molecule 1 (STIM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were determined by western blot analysis. Cell proliferation was assessed by cell colony formation and DNA content quantitation assays. Cell migration and invasion were demonstrated by wound-healing and transwell assays. The putative binding relationships between miR-641 and MIAT or STIM1 were predicted by starbase online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results MIAT and STIM1 expression were substantially upregulated, whereas miR-641 expression was downregulated in ox-LDL-induced VSMCs compared with control groups. Functionally, MIAT silencing attenuated ox-LDL-induced cell proliferation, migration and invasion in VSMCs; however, these effects were impaired by miR-641 inhibitor. STIM1 overexpression also restrained miR-641-mediated impacts on cell proliferation and metastasis under ox-LDL. Mechanistically, MIAT acted as a sponge for miR-641, and miR-641 was associated with STIM1. Conclusions MIAT silencing hindered ox-LDL-induced cell proliferation, migration and invasion by downregulating STIM1 expression through binding to miR-641 in VSMCs. The mechanism provided us with a new target for AS therapy.

Tan IIA mitigates vascular smooth muscle cell proliferation and migration induced by ox‐LDL through the miR‐137/TRPC3 axis

“…ox-LDL stimulation could induce VSMC proliferation and migration, which promotes plaque formation in atherosclerosis. 25,29 Similarly, we also established ox-LDL-induced cellular model, and found Tan IIA could inhibit ox-LDL-induced hyperproliferation and migration of VSMCs. It was also consistent to that under high glucose or homocysteine condition.…”

“…Here we mainly investigated the roles of Tan IIA in VSMC function. ox‐LDL stimulation could induce VSMC proliferation and migration, which promotes plaque formation in atherosclerosis 25,29 …”

Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells

“…Similarly, overexpression of lncRNA HLA complex group 11 (HCG11) can act as a sponge to negatively regulate miR-144 while increasing FOXF1 expression, resulting in increased Bcl-2 and decreased Bax expression, thereby promoting proliferation and inhibiting apoptosis in VSMCs (47). Silencing the lncRNA MIAT acts as a sponge for miR-641, induces stromal interaction molecule 1 (STIM1), attenuates the protein expression of proliferating cell nuclear antigen (PCNA), and Ki-67, and thus inhibits ox-LDL-induced proliferation, migration, and invasion (28). Likewise, overexpression of lncRNA C-terminal binding protein 1-antisense RNA 2 (CTBP1-AS2) acts as a ceRNA for miR-195-5p to promote autophagy-related 14 (ATG14) expression and decrease PCNA and Ki-67 expression levels, thereby inhibiting HAVSMC proliferation (48).…”

miR-1183 Is a Key Marker of Remodeling upon Stretch and Tachycardia in Human Myocardium

“…Finally, it is up-regulated in plasma samples in heart-failure patients [35,36]. miIR-641 is involved in vascular smooth muscle cell proliferation and metastasis [37] and miR-16-1 in cytostatic cardiac injury [38].…”