title: Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells.
abstract: Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis.
authors.affiliation: Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Ling
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xu
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jiang
authors.forename: Bairu
authors.initials: B
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Bian
authors.forename: Qizhan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D018053:Arsenites; C508600:IL6 protein, human; D015850:Interleukin-6; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C015001:arsenite
keywords: Arsenite; Carcinogenesis; Epithelial–mesenchymal transition (EMT); Inflammation