title: Angiogenesis, mediated by miR-21, is involved arsenite-induced carcinogenesis.
abstract: Evidence for arsenite-induced lung cancer in humans is strong, but the molecular mechanisms by which arsenite causes cancer remain to be established. Angiogenesis is a fundamental characteristic of cancer and is necessary in its multi-step progression. In this investigation, the mechanism for arsenite-induced angiogenesis was evaluated. Tumors formed from human bronchial epithelial (HBE) cells transformed by arsenite developed new blood vessels, which were prevented by the knockdown of miR-21, and cultures of human umbilical vein endothelial cells (HUVEC) exposed to arsenite developed endothelial tubes, a characteristic of angiogenesis. Also found in transformed HBE cells were up-regulation of a microRNA, miR-21, and increased levels of vascular endothelial growth factor (VEGF), which promotes angiogenesis. Down-regulation of miR-21 in these cells inhibited the arsenite-induced increases of VEGF levels. Thus, we conclude that arsenite induces tumor angiogenesis through processes mediated by miR-21.
authors.affiliation: Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xu
authors.forename: Bairu
authors.initials: B
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Pang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D018053:Arsenites / Q000506:poisoning*; D015153:Blotting, Western; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D018053:Arsenites; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D012313:RNA; C015001:arsenite
keywords: Angiogenesis; Arsenite; Cancer stem cells; Carcinogenesis; miR-21