Department of Cardiac Surgery, Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Med Hypotheses. 2013 Jul;81(1):108-10. doi: 10.1016/j.mehy.2013.03.043. Epub 2013 Apr 29.
The miR-17-92 cluster is an important microRNA cluster in the animals. It was mainly investigated as an oncogene in tumors but never studied in cardiovascular disease. On one aspect, miR-17-92 cluster is documented to play anti-apoptotic roles in tumor cells, including hypoxia-induced apoptosis. The families of miR-17, miR-19, and miR-92 promote resistance to apoptosis by directly inhibiting pro-apoptotic protein, and by the two major cell survival signaling pathways-PI3K/AKT, and MAPK/ERK. On the other aspect, the component members of miR-17-92 cluster are high expressed in the hearts of canine and mice, suggesting that there are effect targets of the cluster in the myocardium. So that, we hypothesized that the miR-17-92 cluster may protect the heart by diminishing the apoptosis and alleviating ischemia/reperfusion injury. This may be a new regulating target for patients with myocardial infarction and undergoing cardiac surgery.
miR-17-92 簇是动物中重要的 microRNA 簇。它主要作为肿瘤中的癌基因进行研究,但从未在心血管疾病中进行研究。一方面,miR-17-92 簇被证明在肿瘤细胞中发挥抗细胞凋亡作用,包括缺氧诱导的细胞凋亡。miR-17、miR-19 和 miR-92 的家族通过直接抑制促凋亡蛋白和两条主要的细胞存活信号通路-PI3K/AKT 和 MAPK/ERK,来促进细胞凋亡抵抗。另一方面,miR-17-92 簇的组成成员在犬和鼠的心脏中高表达,这表明该簇在心肌中有作用靶点。因此,我们假设 miR-17-92 簇可能通过减少细胞凋亡和减轻缺血/再灌注损伤来保护心脏。这可能为心肌梗死和接受心脏手术的患者提供一个新的调节靶点。