Fan Jianmin, Zhang Wen, Liu Qiming
The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410007, China.
Cardiovascular Medicine Department, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Biomed Res Int. 2014;2014:531979. doi: 10.1155/2014/531979. Epub 2014 May 8.
Human cytomegalovirus (HCMV) infection is linked to the development and severity of the cardiovascular disease atherosclerosis; however, there is little known about the promotion of atherosclerosis. miR-US25-1 is one of HCMV-encoded miRNAs and targets cellular genes that are essential for virus growth to control the life cycle of the virus and host cells. The prominent regulation on cell cycle genes of the miR-US25-1 attracts us to explore its role in the atherosclerosis promotion. It was indicated that miR-US25-1 level was upregulated in subjects or in endothelial cells with HCMV infection; and the miR-US25-1 downregulated the expression of BRCC 3 by targeting the 5' UTR of BRCC 3. And a miR-US25-1 mimics transfection could reduce the EAhy926 cell viability but did not induce apoptosis in EAhy926 cells. And what is more, miR-US25-1 mimicis transfection deteriorated the ox-LDL-induced apoptosis and aggravated the upregulation of apoptosis-associated molecules by oxidised low density lipoprotein (ox-LDL) in EAhy926 cells. And we have also confirmed the deregulation of BRCC 3 expression by miR-US25-1 by targeting the 5' UTR of it. Given the vital role of BRCC 3 in DNA damage repairing, we speculated that the targeting inhibition of BRCC 3 by miR-US25-1 may contribute to the aggravation of ox-LDL-promoted apoptosis of endothelial EAhy926 cells.
人类巨细胞病毒(HCMV)感染与心血管疾病动脉粥样硬化的发生和严重程度有关;然而,关于其促进动脉粥样硬化的机制知之甚少。miR-US25-1是HCMV编码的miRNA之一,靶向病毒生长所必需的细胞基因以控制病毒和宿主细胞的生命周期。miR-US25-1对细胞周期基因的显著调控吸引我们探索其在促进动脉粥样硬化中的作用。研究表明,在HCMV感染的受试者或内皮细胞中,miR-US25-1水平上调;miR-US25-1通过靶向BRCC 3的5'UTR下调其表达。转染miR-US25-1模拟物可降低EAhy926细胞活力,但不会诱导EAhy926细胞凋亡。此外,转染miR-US25-1模拟物会使氧化型低密度脂蛋白(ox-LDL)诱导的EAhy926细胞凋亡恶化,并加重氧化型低密度脂蛋白(ox-LDL)引起的凋亡相关分子的上调。我们还通过靶向BRCC 3的5'UTR证实了miR-US25-1对其表达的调控失调。鉴于BRCC 3在DNA损伤修复中的重要作用,我们推测miR-US25-1对BRCC 3的靶向抑制可能导致内皮EAhy926细胞中ox-LDL促进的凋亡加剧。