Department of Emergency Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Department of General Medicine, Jiangsu Province Official Hospital, Nanjing, China.
IUBMB Life. 2017 Nov;69(11):877-886. doi: 10.1002/iub.1686. Epub 2017 Oct 16.
miR-200c is an antioncogene in multiple tumors. However, its function in the pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly investigated nor understood. In this study, we discovered that miR-200c was able to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs) treated with endothelin-1 (ET-1). miR-200c also induced cell proliferation and suppressed cell apoptosis in PASMCs in vitro. However, miR-200c had no effect on G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR-200c as a new regulator of the microtubule associated protein 2 (MAP-2) and zinc finger E-box binding homeobox1 (ZEB-1) in PASMCs. miR-200c inhibited MAP-2 and ZEB-1 expression by directly binding to their 3'-untranslated regions(3'UTR) according to luciferase assay results. Our findings provide novel insights into the mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH diagnosis and treatment. © 2017 IUBMB Life, 69(11):877-886, 2017.
miR-200c 是多种肿瘤的抑癌基因。然而，其在肺动脉高压（PAH）发病机制中的作用尚未得到深入研究和理解。在本研究中，我们发现内皮素-1（ET-1）处理的肺动脉平滑肌细胞（PASMCs）中能够显著上调 miR-200c。miR-200c 还能在体外诱导 PASMCs 增殖并抑制细胞凋亡。然而，miR-200c 对细胞周期中的 G1/S/G2 转变没有影响。此外，我们鉴定出 miR-200c 是 PASMCs 中微管相关蛋白 2（MAP-2）和锌指 E 盒结合同源框 1（ZEB-1）的新调节因子。根据荧光素酶检测结果，miR-200c 通过直接结合其 3'-非翻译区（3'UTR）抑制 MAP-2 和 ZEB-1 的表达。我们的研究结果为 PAH 发病机制的机制提供了新的见解，并为 PAH 的诊断和治疗提供了潜在的分子生物标志物。©2017 IUBMB Life，69（11）：877-886，2017。
