4.7 Article

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

期刊

JOURNAL OF PATHOLOGY
卷 232, 期 3, 页码 330-343

出版社

WILEY
DOI: 10.1002/path.4295

关键词

miR-199a-5p; VEGFA; endometriosis; endometrial mesenchymal stem cells

资金

  1. Kaohsiung Medical University Hospital Research Fund [KMUH-99-9I04, KMUH101-1R27, KMUH100-0R24]
  2. National Science Council, Taiwan [NSC102-2628-B-037-011-MY3, 102-2632-B-037-001-MY3]
  3. National Sun Yat-Sen University-KMU Joint Research Project [NSYSUKMU 102-P029]

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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.

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