NEAT1/miR-140-3p/MAPK1 mediates the viability and survival of coronary endothelial cells and affects coronary atherosclerotic heart disease

Abstract

Studies have shown that long non-coding RNAs (lncRNA) play critical roles in coronary atherosclerotic heart disease (CAD). However, the function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in CAD is unclear. In this study, we aimed to investigate the functions of lncRNA NEAT1 in CAD. RT-PCR and western blot analysis were carried out to examine the expressions of related RNAs. Colony formation assay, cell proliferation assay, apoptosis assay, and dual-luciferase reporter assay were conducted to investigate the abilities of colony migration, cell proliferation, apoptosis, and targeting. The results showed that NEAT1 was up-regulated in CAD blood samples and in human coronary endothelial cells (HCAECs). Transfection of pcNEAT1 significantly inhibited the survival rate of HCAECs and induced apoptosis of HCAECs. MiR-140-3p was down-regulated in HCAECs. NEAT1 directly targeted miR-140-3p, and the expression of miR-140-3p was inversely correlated with the expression of NEAT1 in CAD patients. In addition, co-transfection of NEAT1 with miR-140-3p mimic reversed the effect of pcNEAT1 on cell viability and apoptosis. mitogen-activated protein kinase 1 (MAPK1) was proved to be a target gene of miR-140-3p, and the miR-140-3p mimic was shown to reduce the expression of MAPK1 in HCAECs. pcNEAT1 significantly increased the expression level of MAPK1, while shNEAT1 significantly reduced the expression level of MAPK1. Our results revealed that lncRNA NEAT1 increased cell viability and inhibited CAD cell apoptosis possibly by activating the miR-140-3p/MAPK1 pathway, and lncRNA NEAT1 might serve as a potential therapeutic target for CAD.

Dysregulation of serum miR-361-5p serves as a biomarker to predict disease onset and short-term prognosis in acute coronary syndrome patients

“…For example, miR-223-3p could alleviate vascular endothelial injury in kawasaki disease [37]. NEAT1/ miR-140-3p/MAPK1 mediated the viability and survival of coronary endothelial cells and affected coronary atherosclerotic heart disease [38]. MiR-17 regulated the proliferation and apoptosis of endothelial cells in CHD [39].…”

Role of competitive endogenous RNA networks in the pathogenesis of coronary artery disease

“…MAPK1 is a protein-coding gene with transferase activity and tyrosine kinase activity that is involved in the transfer of phosphorus-containing groups in signaling pathways. Studies have shown that MAPK1 is upregulated by miR-140-3p and inhibits CAD cell apoptosis (33). Knockout of ABL1 gene inhibits c-Abl activity and significantly reduces apoptosis of VSMCs and synthetic phenotypic transformation induced by Ang II both in vivo and in vitro (34).…”

Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Zhongfeng Xingnao Formula against Intracerebral Hemorrhage

“…Sun et al indicated that RELA, a key transcription factor for hypoxic response, can promote the expression of CXCL12 under hypoxic conditions by combining with LINC01693 and thus promote hypoxia-induced angiogenesis [46]. MAPK1, belonging to the MAPK family, can be activated by LncRNA NEAT1 to enhance cell viability and inhibit cell apoptosis [47]. Wei et al illustrated that the methylation of the TP53 promoter may be related to the occurrence of atherosclerosis ,which has got wider audience in the research of atherosclerosis [48].…”