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miRNA‐199a‐5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis
Authors:Chia‐Yi Hsu  Tsung‐Hua Hsieh  Cheng‐Fang Tsai  Hung‐Pei Tsai  Hung‐Sheng Chen  Yu Chang  Hui‐Yu Chuang  Jau‐Nan Lee  Ya‐Ling Hsu  Eing‐Mei Tsai
Affiliation:1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, , Kaohsiung City, Taiwan, Republic of China;2. Department of Obstetrics and Gynaecology, Kaohsiung Medical University Hospital, , Kaohsiung City, Taiwan, Republic of China;3. Center for Resources, Research and Development, Kaohsiung Medical University, , Kaohsiung City, Taiwan, Republic of China
Abstract:
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 © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Keywords:miR‐199a‐5p  VEGFA  endometriosis  endometrial mesenchymal stem cells
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