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2064223 
Journal Article 
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 
Luo, F; Xu, Y; Ling, M; Zhao, Y; Xu, W; Liang, X; Jiang, R; Wang, B; Bian, Q; Liu, Q 
In Press 
Yes 
Toxicology and Applied Pharmacology
ISSN: 0041-008X
EISSN: 1096-0333 
273 
27-34 
English 
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. 
Inflammation; Epithelial-mesenchymal transition (EMT); Arsenite; Carcinogenesis 
IRIS
• Arsenic Hazard ID
          PubMed
          Considered New
          PubMed
          ToxNet
          Considered New
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
     2. Lit Search Updates through Oct 2015
          PubMed
          WOS
          ToxNet
          Considered
     7. Other Studies through Oct 2015
          MOA
• Arsenic (Inorganic)
     1. Literature
          Lit search updates through Oct 2015
     3. Hazard ID Screening
          Other potentially supporting studies
     4. Adverse Outcome Pathways/Networks Screening
          Relevant
• Arsenic MOA
     4. Adverse Outcome Pathways
          Cellular differentiation and malignant transformation
          Regenerative proliferation
     5. Health Effect
          Cancer
     1. MOA Literature Screening
          Health Effect Screening