title: MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor.
abstract: Recurrent spontaneous abortion (RSA) is a common health problem that affects women of reproductive age. Recent studies have indicated that microRNAs are important factors in miscarriage. This study investigated the role of miR-16 in regulating vascular endothelial growth factor (VEGF) expression and the pathogenesis of RSA. In this report, clinical samples revealed that miR-16 expression was significantly elevated in the villi and decidua of RSA patients. In vitro, miR-16 upregulation inhibited human umbilical vein endothelial cell proliferation, migration and tube formation. Conversely, the downregulation of miR-16 reversed these effects. In vivo, we demonstrated that abnormal miR-16 levels affect the weights of the placenta and embryo and the number of progeny and microvascular density, as well as cause recurrent abortions by controlling VEGF expression in pregnant mice. VEGF, a potential target gene of miR-16, was inversely correlated with miR-16 expression in the decidua of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-16 was found to directly downregulate the expression of VEGF by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-16 regulates placental angiogenesis and development by targeting VEGF expression and is involved in the pathogenesis of RSA.
authors.affiliation: Xi'an Jiao Tong University, College of Forensic Science, Xi'an, Shaanxi, PR China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Zhanbin
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dang
authors.affiliation: Xi'an Mental Health Center, The Sixth Ward, Xi'an, Shaanxi, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dang
authors.affiliation: General Hospital of Ningxia Medical University, Department of Clinical Laboratory, Yinchuan, Ningxia, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics, Department of Medical Genetic and Cell Biology, Yinchuan, Ningxia, PR China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003656:Decidua / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010929:Placentation / Q000235:genetics; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A