miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis

被引:165
作者
Hsu, Chia-Yi [1 ]
Hsieh, Tsung-Hua [2 ]
Tsai, Cheng-Fang [1 ]
Tsai, Hung-Pei [1 ]
Chen, Hung-Sheng [2 ]
Chang, Yu [2 ]
Chuang, Hui-Yu [2 ]
Lee, Jau-Nan [2 ]
Hsu, Ya-Ling [1 ]
Tsai, Eing-Mei [1 ,2 ,3 ]
机构
[1] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung 807, Taiwan
[2] Kaohsiung Med Univ Hosp, Dept Obstet & Gynaecol, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Ctr Resources Res & Dev, Kaohsiung 807, Taiwan
关键词
miR-199a-5p; VEGFA; endometriosis; endometrial mesenchymal stem cells; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CIRCULATING MICRORNAS; GENE-EXPRESSION; CANCER CELLS; GROWTH; MIR-199A; OVEREXPRESSION; PROLIFERATION; INVASIVENESS; ANGIOGENESIS;
D O I
10.1002/path.4295
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3 untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:330 / 343
页数:14
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