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Dysregulation of MiR-199a/IL8 pathway in chronic Cr (VI)-induced tumor growth and angiogenesis

Authors :
Lin Wang
Zhi-Hao Zhou
Yun-Xia Xie
Wen-Jing Liu
Rui-Xiang Zhang
Nan Jiang
Ming-Liang He
Jian-Ge Qiu
Bing-Hua Jiang
Source :
Ecotoxicology and Environmental Safety, Vol 262, Iss , Pp 115155- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.

Details

Language :
English
ISSN :
01476513
Volume :
262
Issue :
115155-
Database :
Directory of Open Access Journals
Journal :
Ecotoxicology and Environmental Safety
Publication Type :
Academic Journal
Accession number :
edsdoj.9e7dee809eb244cda5c54d93bb7bb7d8
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ecoenv.2023.115155