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Toxicol Appl Pharmacol. 2013 Nov 15;273(1):27-34. doi: 10.1016/j.taap.2013.08.025. Epub 2013 Sep 1.

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.

Author information

  • 1Institute 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.

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.

KEYWORDS:

Arsenite; Carcinogenesis; Epithelial–mesenchymal transition (EMT); Inflammation

PMID:
24004609
DOI:
10.1016/j.taap.2013.08.025
[PubMed - indexed for MEDLINE]
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