Jump to main content
Jump to site search

Issue 1, 2016
Previous Article Next Article

HIF-2α, acting via miR-191, is involved in angiogenesis and metastasis of arsenite-transformed HBE cells

Author affiliations

Abstract

Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested that hypoxia-inducible factors (HIFs) and microRNAs (miRNAs) are involved in human lung cancer; however, their molecular mechanisms that causally contribute to arsenite-caused malignant transformation of cells remain unclear. To elucidate the mechanisms of angiogenesis and metastasis of lung cancer caused by arsenite, we investigated the role of HIF-2α regulation of miRNA-191 (miR-191) in the angiogenic and metastatic properties of human bronchial epithelial (HBE) cells transformed by arsenite. In HBE cells, HIF-2α binds to the hypoxia response element (HRE) in the promoter region of miR-191 and initiates transcription of miR-191. Blocking of HIF-2α with siRNA inhibited the up-regulation of miR-191, Wilms’ tumor 1 (WT1) protein, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and the down-regulation of brain acid-soluble protein 1 (BASP1). In arsenite-transformed HBE (T-HBE) cells, down-regulation of HIF-2α by siRNA blocked the process of angiogenesis and decreased their neoplastic properties and metastatic capacity, which were reversed by over-expression of miR-191 or by up-regulating WT1. Thus, HIF-2α up-regulates WT1 via miR-191, both of which are involved in the angiogenesis and metastasis of T-HBE cells. The results present a better understanding of the processes involved in lung cancer caused by arsenite exposure.

Graphical abstract: HIF-2α, acting via miR-191, is involved in angiogenesis and metastasis of arsenite-transformed HBE cells

Back to tab navigation

Supplementary files

Publication details

The article was received on 10 Jul 2015, accepted on 02 Nov 2015 and first published on 06 Nov 2015


Article type: Paper
DOI: 10.1039/C5TX00225G
Citation: Toxicol. Res., 2016,5, 66-78
  •   Request permissions

    HIF-2α, acting via miR-191, is involved in angiogenesis and metastasis of arsenite-transformed HBE cells

    W. Xu, F. Luo, B. Sun, H. Ye, J. Li, L. Shi, Y. Liu, X. Lu, B. Wang, Q. Wang, Q. Liu and A. Zhang, Toxicol. Res., 2016, 5, 66
    DOI: 10.1039/C5TX00225G

Search articles by author

Spotlight

Advertisements