Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway.

Authors

Jun He, Department of Pathology, Nanjing Medical University, Nanjing, People’s Republic of ChinaFollow
Min Wang, Department of Pathology, Nanjing Medical University, Nanjing, People’s Republic of ChinaFollow
Yue Jiang, College of Life Sciences, Fujian Normal University, People’s Republic of ChinaFollow
Qiudan Chen, Department of Pathology, Nanjing Medical University, Nanjing, People’s Republic of ChinaFollow
Shaohua Xu, Changzhou Maternal and Child Care Hospital, Changzhou, People’s Republic of ChinaFollow
Qing Xu, Thomas Jefferson UniversityFollow
Bing-Hua Jiang, Thomas Jefferson UniversityFollow
Ling-Zhi Liu, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

3-1-2014

Comments

This article has been peer reviewed. It was published in Environmental Health Perspectives.

Volume 122, Issue 3, March 2014, Pages: 255-261.

The published version is available at DOI: 10.1289/ehp.1307545. Copyright © National Institute of Environmental Health Sciences (NIEHS)

Abstract

Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood.Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth.Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis.Results: We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis.Conclusion: The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis.Citation: He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255-261; http://dx.doi.org/10.1289/ehp.1307545.

Recommended Citation

He, Jun; Wang, Min; Jiang, Yue; Chen, Qiudan; Xu, Shaohua; Xu, Qing; Jiang, Bing-Hua; and Liu, Ling-Zhi, "Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway." (2014). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 146.
https://jdc.jefferson.edu/pacbfp/146

PubMed ID

24413338