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

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• 作者：Fei Luo ; Yuan Xu ; Min Ling ; Yue Zhao ; Wenchao Xu ; Xiao Liang ; Rongrong Jiang ; Bairu Wang ; Qian Bian ; Qizhan Liu
• 关键词：Inflammation ; Epithelial&ndash ; mesenchymal transition (EMT) ; Arsenite ; Carcinogenesis
• 刊名：Toxicology and Applied Pharmacology
• 出版年：15 November, 2013
• 年：2013
• 卷：273
• 期：1
• 页码：27-34
• 全文大小：1182 K

文摘

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 3 days, 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.