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Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway.
In: Environmental Health Perspectives, Jg. 122 (2014-03-01), Heft 3, S. 255-261
Online
academicJournal
Zugriff:
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 arsenictransformed 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. [ABSTRACT FROM AUTHOR]
Titel: |
Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway.
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Autor/in / Beteiligte Person: | He, Jun ; Wang, Min ; Jiang, Yue ; Chen, Qiudan ; Xu, Shaohua ; Xu, Qing ; Jiang, Bing-Hua ; Liu, Ling-Zhi |
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Zeitschrift: | Environmental Health Perspectives, Jg. 122 (2014-03-01), Heft 3, S. 255-261 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 0091-6765 (print) |
DOI: | 10.1289/ehp.1307545 |
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