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

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

doi:10.1016/j.ecoenv.2023.115155

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

Ecotoxicol Environ Saf. 2023 Jun 19:262:115155. doi: 10.1016/j.ecoenv.2023.115155. Online ahead of print.

Authors

Lin Wang¹, Zhi-Hao Zhou¹, Yun-Xia Xie¹, Wen-Jing Liu², Rui-Xiang Zhang³, Nan Jiang⁴, Ming-Liang He⁵, Jian-Ge Qiu⁶, Bing-Hua Jiang⁷

Affiliations

¹ The First Affiliated Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China.
² The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China.
³ Department of Thoracic Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁴ Department of Thoracic Surgery, Affiliated Chest Hospital of Zhengzhou University, Zhengzhou 450000, China.
⁵ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
⁶ The First Affiliated Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China. Electronic address: jiangeqiu@zzu.edu.cn.
⁷ The First Affiliated Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China. Electronic address: binghjiang@zzu.edu.cn.

PMID: 37343486
DOI: 10.1016/j.ecoenv.2023.115155

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.

Keywords: Angiogenesis; Cr (VI); IL8; MiR-199a; Tumor growth.