title: MiR-195 participates in the placental disorder of preeclampsia via targeting activin receptor type-2B in trophoblastic cells.
abstract: Preeclampsia is a pregnancy-related syndrome. Shallow invasion of uterine wall by trophoblast cells has been generally accepted as the major pathological change of this disorder. We previously found downregulation of miR-195 in preeclamptic placentas. Bioinformatic analysis predicted a type II activin receptor, activin receptor type-2B (ActRIIB), as one of the potential targets of miR-195. Considering the key function of activin A on trophoblast cell behaviors and placenta development, we proposed miR-195 may affect trophoblast cell invasion by repressing the expression of ActRIIB.
  
  
  
  The colocalization of ActRIIB and miR-195 in human placenta was measured by in-situ hybridization and immunohistochemistry. Western blotting, real-time PCR and dual luciferase assay were performed in human trophoblast cell line, HTR8/SVneo cells, to validate the targeting of ActRIIB by miR-195. Cell invasiveness was analyzed using transwell insert invasion assay in HTR8/SVneo cells.
  
  
  
  In human placenta, ActRIIB and miR-195 exhibited similar localization in various subtypes of trophoblast cells, including villous and extravillous trophoblasts. The protein expressions of ActRIIB in preeclamptic placenta were significantly higher as compared with the normal controls, which was opposite to the changing pattern of miR-195. In HTR8/SVneo cells, miR-195 could directly target and suppress the expression of ActRIIB. Meanwhile, the invasion-promoting effect of miR-195 on trophoblast cells could be largely impeded by ActRIIB overexpression.
  
  
  
  In human trophoblast cells, miR-195 could promote cell invasion via directly targeting ActRIIB. The impaired miR-195 expression may contribute to the occurrence or development of preeclampsia through interfering with activin/nodal signaling in the placenta.
authors.affiliation: aDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou bDepartment of Obstetric and Gynecology, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine cState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences dUniversity of Chinese Academy of Sciences, Beijing, China eDepartment of Biology, York University, Toronto, Ontario, Canada *HWu and HWang contributed equally to the writing of this article.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Ji
authors.forename: Chun
authors.initials: C
authors.lastname: Peng
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Yu
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wang
mesh_terms: D030301:Activin Receptors, Type II / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000502:physiology*
chemical_list: C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B