We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Repression of miR-143 Mediates Cr (VI)–Induced Tumor Angiogenesis via IGF-IR/IRS1/ERK/IL-8 Pathway.
- Authors
He, Jun; Qian, Xu; Carpenter, Richard; Xu, Qing; Wang, Lin; Qi, Yanting; Wang, Zi-Xuan; Liu, Ling-Zhi; Jiang, Bing-Hua
- Abstract
Hexavalent chromium [Cr (VI)] is a well-known human carcinogen associated with the increased risk of lung cancer. However, the mechanism underlying the Cr (VI)–induced carcinogenesis remains unclear due to the lack of suitable experimental models. In this study, we developed an in vitro model by transforming nontumorigenic human lung epithelial BEAS-2B cells through long-term exposure to Cr (VI). By utilizing this model, we found that miR-143 expression levels were dramatically repressed in Cr (VI)–transformed cells. The repression of miR-143 led to Cr (VI)–induced cell malignant transformation and angiogenesis via upregulation of insulin-like growth factor-1 receptor (IGF-IR) and insulin receptor substrate-1 (IRS1) expression. Moreover, we found that interleukin-8 is the major upregulated angiogenesis factor induced by Cr (VI) through activation of IGF-IR/IRS1 axis followed by activation of downstream ERK/hypoxia-induced factor-1α/NF-κB signaling pathway. These findings establish a causal role and mechanism of miR-143 in regulating Cr (VI)–induced malignant transformation and tumor angiogenesis.
- Subjects
NEOVASCULARIZATION; TUMOR blood vessels; HEXAVALENT chromium toxicology; LUNG cancer risk factors; GENE expression; ONCOGENIC viruses
- Publication
Toxicological Sciences, 2013, Vol 134, Issue 1, p26
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kft101