Shan K, Jiang Q, Wang X-Q, Wang Y-N-Z, Yang H, Yao M-D, Liu C, Li X-M, Yao J, Liu B, Zhang Y-Y, J Yong, Yan B
Eye Hospital, Nanjing Medical University, Nanjing, China.
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
Cell Death Dis. 2016 Jun 2;7(6):e2248. doi: 10.1038/cddis.2016.145.
Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction.
动脉粥样硬化是最常见的血管疾病之一。内皮细胞（EC）功能障碍和血管平滑肌细胞（VSMC）增殖促成了动脉粥样硬化的发展。长链非编码RNA（lncRNA）已涉及多种生物学过程和人类疾病。在此我们表明lncRNA-RNCR3在EC和VSMC中表达。在小鼠和人类主动脉粥样硬化病变中，以及体外经氧化型低密度脂蛋白（ox-LDL）处理的培养EC和VSMC中，RNCR3表达显著上调。在体内，敲低RNCR3会加速动脉粥样硬化的发展，加重高胆固醇血症和炎性因子释放，并减少EC和VSMC增殖。敲低RNCR3在体外也会降低EC和VSMC的增殖与迁移，并加速其凋亡进程。RNCR3作为一种竞争性内源RNA（ceRNA），与Kruppel样因子2和miR-185-5p形成反馈环以调节细胞功能。本研究揭示RNCR3在动脉粥样硬化中具有抗动脉粥样硬化作用，对其进行干预是治疗动脉粥样硬化相关血管功能障碍的一种有前景的策略。
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