title: MicroRNA-141-3p and miR-200a-3p regulate insulin-like growth factor 2 during mouse placental development.
abstract: Insulin-like growth factor 2 (IGF2) plays a vital role in fetal and placental development throughout gestation. Placental expression of IGF2 decreases substantially in intra-uterine growth restriction (IUGR) and Igf2 null mice develop small placentas. In this report, we examined the role of microRNAs in regulating Igf2 gene expression during mouse placental development. Using bioinformatic analysis, we have identified microRNAs that have conserved binding sites in the 3'-UTR of Igf2. Using luciferase reporter assay, we demonstrated that miR141-3p and miR-200a-3p mimics substantially down regulated relative luciferase activity by binding to 3'-UTR of Igf2, which was reversed by using miR141-3p and miR-200a-3p inhibitors. Furthermore, in a similar assay, use of Igf2 3'-UTR that lacked the binding site for the microRNAs did not have any effect on luceiferase activity. Interestingly, the expression of miR141-3p and miR-200a-3p were inversely and temporally correlated to the expression of IGF2 during mouse placental development. Overexpression of miR141-3p and miR-200a-3p in mouse trophoblast stem cells suppressed endogenous expression of IGF2. Consequently, IGF2 silencing by miR141-3p and miR-200a-3p diminished Akt activation in mouse trophoblast stem cells. Our study provides evidence for regulation of Igf2 by microRNAs and further elucidates the role of miR141-3p and miR-200a-3p in the mouse placental development.
authors.affiliation: Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
authors.forename: Sarbani
authors.initials: S
authors.lastname: Saha
authors.affiliation: Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
authors.forename: Jaganmoy
authors.initials: J
authors.lastname: Choudhury
authors.affiliation: Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India. Electronic address: rupasri@iicb.res.in.
authors.forename: Rupasri
authors.initials: R
authors.lastname: Ain
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000196:embryology*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C513121:IGF2 protein, mouse; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; C543719:Mirn200 microRNA, mouse; D007335:Insulin-Like Growth Factor II
keywords: IGF2; Placenta; Pregnancy; Trophoblast; microRNA