title: miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis.
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.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of China.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Hsu
authors.forename: Tsung-Hua
authors.initials: TH
authors.lastname: Hsieh
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.forename: Hung-Pei
authors.initials: HP
authors.lastname: Tsai
authors.forename: Hung-Sheng
authors.initials: HS
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Chuang
authors.forename: Jau-Nan
authors.initials: JN
authors.lastname: Lee
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000818:Animals; D047369:Chromatin Immunoprecipitation; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C531408:mirn199 microRNA, human
keywords: VEGFA; endometrial mesenchymal stem cells; endometriosis; miR-199a-5p