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.

中文翻译：

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NEAT1 / miR-140-3p / MAPK1介导冠状动脉内皮细胞的生存能力和存活率，并影响冠状动脉粥样硬化性心脏病。

研究表明，长的非编码RNA（lncRNA）在冠状动脉粥样硬化性心脏病（CAD）中起关键作用。但是，尚不清楚lncRNA富核转录本1（NEAT1）在CAD中的功能。在这项研究中，我们旨在研究lncRNA NEAT1在CAD中的功能。进行RT-PCR和蛋白质印迹分析以检查相关RNA的表达。进行了菌落形成测定，细胞增殖测定，凋亡测定和双荧光素酶报告基因测定，以研究菌落迁移，细胞增殖，凋亡和靶向的能力。结果表明，CAD血样和人冠状动脉内皮细胞（HCAEC）中的NEAT1上调。pcNEAT1的转染显着抑制了HCAEC的存活率并诱导了HCAEC的凋亡。在HCAEC中，MiR-140-3p被下调。NEAT1直接靶向miR-140-3p，在CAD患者中miR-140-3p的表达与NEAT1的表达呈负相关。此外，NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。NEAT1直接靶向miR-140-3p，而miR-140-3p的表达与CAD患者中NEAT1的表达呈负相关。此外，NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。NEAT1直接靶向miR-140-3p，而miR-140-3p的表达与CAD患者中NEAT1的表达呈负相关。此外，NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。在CAD患者中，miR-140-3p的表达与NEAT1的表达呈负相关。此外，NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。在CAD患者中，miR-140-3p的表达与NEAT1的表达呈负相关。此外，NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。NEAT1与miR-140-3p模拟物的共转染逆转了pcNEAT1对细胞活力和细胞凋亡的影响。丝裂原激活的蛋白激酶1（MAPK1）被证明是miR-140-3p的靶基因，而miR-140-3p模仿物显示可降低HCAECs中MAPK1的表达。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。pcNEAT1显着增加MAPK1的表达水平，而shNEAT1显着降低MAPK1的表达水平。我们的结果表明，lncRNA NEAT1可能通过激活miR-140-3p / MAPK1途径来提高细胞活力并抑制CAD细胞凋亡，而lncRNA NEAT1可能成为CAD的潜在治疗靶标。