Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China.
Department of Gastroenterology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China.
J Cell Biochem. 2018 Mar;119(3):2797-2805. doi: 10.1002/jcb.26448. Epub 2017 Nov 24.
Atherosclerosis is the major cause of stroke and heart disease. However, the course and pathogenesis of atherosclerosis remains unknown. The proliferation and migration of endothelial cell play important roles in the inition and pathological progression of atherosclerosis. In this study, we demonstrated that long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression level was higher in coronary artery disease (CAD) tissues than in normal arterial tissues. The expression level of HOTTIP was upregulated in the proliferating endothelial cells induced by TNF-α or PDGF-BB. Ectopic expression of HOTTIP promoted endothelial cell proliferation and also increased the expression of proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP promoted endothelial cell migration. Downregulation expression of HOTTIP suppressed endothelial cell proliferation and migration. Furthermore, we determined that overexpression of HOTTIP induced β-catenin expression and enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic expression of HOTTIP increased endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.
动脉粥样硬化是中风和心脏病的主要原因。然而，动脉粥样硬化的病程和发病机制仍不清楚。内皮细胞的增殖和迁移在动脉粥样硬化的起始和病理进展中起着重要作用。在这项研究中，我们证明长链非编码 RNA（lncRNA）HOXA 转录远端末端（HOTTIP）在冠状动脉疾病（CAD）组织中的表达水平高于正常动脉组织。HOTTIP 的表达水平在 TNF-α或 PDGF-BB 诱导的增殖内皮细胞中上调。HOTTIP 的异位表达促进内皮细胞增殖，并增加增殖标志物细胞周期蛋白 D1 和 PCNA 的表达。此外，HOTTIP 的高表达促进内皮细胞迁移。HOTTIP 的下调表达抑制内皮细胞增殖和迁移。此外，我们确定过表达 HOTTIP 诱导内皮细胞中β-连环蛋白表达，并增强下游蛋白 c-Myc 表达。HOTTIP 的异位表达通过激活 Wnt/β-连环蛋白通路增加内皮细胞的增殖和迁移。这些结果表明，HOTTIP 可能通过激活 Wnt/β-连环蛋白通路来操纵内皮细胞的增殖和迁移。
