title: MicroRNA-181b and microRNA-9 mediate arsenic-induced angiogenesis via NRP1.
abstract: Environmental exposure to inorganic arsenic compounds has been reported to have serious health effects on humans. Recent studies reported that arsenic targets endothelial cells lining blood vessels, and endothelial cell activation or dysfunction, may underlie the pathogenesis of arsenic-induced diseases and developmental toxicity. It has been reported that microRNAs (miRNAs) may act as an angiogenic switch by regulating related genes. The present study was designed to test the hypothesis that arsenite-regulated miRNAs play pivotal roles in arsenic-induced toxicity. Fertilized eggs were injected via the yolk sac with 100  nM sodium arsenite at Hamburger-Hamilton (HH) stages 6, 9, and 12, and harvested at HH stage 18. To identify the individual miRNAs and mRNAs that may regulate the genetic network, the expression profiles of chick embryos were analyzed by microarray analysis. Microarray analyses revealed that the expression of a set of miRNAs changed after arsenite administration, especially miRNA-9, 181b, 124, 10b, and 125b, which exhibited a massive decrease in expression. Integrative analyses of the microarray data revealed that several miRNAs, including miR-9 and miR-181b, might target several key genes involved in arsenic-induced developmental toxicity. A luciferase reporter assay confirmed neuropilin-1 (Nrp1) as a target of mir-9 and mir-181b. Data from the transwell migration assay and the tube-formation assay indicated that miR-9 and mir-181b inhibited the arsenic-induced EA.hy926 cell migration and tube formation by targeting NRP1. Our study demonstrates that the environmental toxin, sodium arsenite, induced angiogenesis by altering the expression of miRNAs and their cognate mRNA targets.
authors.affiliation: Department of Genetics, Graduate School of Peking Union Medical College, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.forename: Zhongji
authors.initials: Z
authors.lastname: Han
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Hao
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xia
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D004785:Environmental Pollutants / Q000633:toxicity; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D018053:Arsenites; D004785:Environmental Pollutants; D035683:MicroRNAs; D012333:RNA, Messenger; D017670:Sodium Compounds; D039942:Neuropilin-1; C017947:sodium arsenite