globalchange  > 气候变化事实与影响
DOI: 10.1289/ehp.1307545
论文题名:
Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway
作者: Jun He; 1; 2 Min Wang; 1 Yue Jiang; 3 Qiudan Chen; 1 Shaohua Xu; 4 Qing Xu; 2 Bing-Hua Jiang; 1; 2; Ling-Zhi Liu2
刊名: Environmental Health Perspectives
ISSN: 0091-7393
出版年: 2014
卷: Volume 122, 期:Issue 3
起始页码: 255
语种: 英语
英文摘要: 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.
URL: https://ehp.niehs.nih.gov/1307545
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/12722
Appears in Collections:气候变化事实与影响
气候变化与战略

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作者单位: 1State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; 3Faculty of Software, College of Life Sciences, Fujian Normal University, People’s Republic of China; 4Changzhou Maternal and Child Care Hospital, Changzhou, People’s Republic of China

Recommended Citation:
Jun He,1,2 Min Wang,et al. Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway[J]. Environmental Health Perspectives,2014-01-01,Volume 122(Issue 3):255
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