None of the authors have any conflicts of interest. The corresponding author has full access to all the data in the study and has the final responsibility for the decision to submit for publication.
Original Research Article
Article first published online: 23 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 2, pages 772–783, February 2012
How to Cite
Cui, Y., Han, Z., Hu, Y., Song, G., Hao, C., Xia, H. and Ma, X. (2012), MicroRNA-181b and microRNA-9 mediate arsenic-induced angiogenesis via NRP1. J. Cell. Physiol., 227: 772–783. doi: 10.1002/jcp.22789
Yi Cui and Zhongji Han contributed equally to this work.
- Issue published online: 23 NOV 2011
- Article first published online: 23 NOV 2011
- Accepted manuscript online: 18 APR 2011 08:26AM EST
- Manuscript Accepted: 31 MAR 2011
- Manuscript Received: 18 DEC 2010
- National Basic Research Program of China. Grant Number: 2007CB511905
- Natural Science Foundation of China. Grant Number: 30800396
Environmental exposure to inorganic arsenic compounds has been reported to have serious health effects on humans. Recent studies reported that arsenic targets endothelial cells lining blood vessels, and endothelial cell activation or dysfunction, may underlie the pathogenesis of arsenic-induced diseases and developmental toxicity. It has been reported that microRNAs (miRNAs) may act as an angiogenic switch by regulating related genes. The present study was designed to test the hypothesis that arsenite-regulated miRNAs play pivotal roles in arsenic-induced toxicity. Fertilized eggs were injected via the yolk sac with 100 nM sodium arsenite at Hamburger–Hamilton (HH) stages 6, 9, and 12, and harvested at HH stage 18. To identify the individual miRNAs and mRNAs that may regulate the genetic network, the expression profiles of chick embryos were analyzed by microarray analysis. Microarray analyses revealed that the expression of a set of miRNAs changed after arsenite administration, especially miRNA-9, 181b, 124, 10b, and 125b, which exhibited a massive decrease in expression. Integrative analyses of the microarray data revealed that several miRNAs, including miR-9 and miR-181b, might target several key genes involved in arsenic-induced developmental toxicity. A luciferase reporter assay confirmed neuropilin-1 (Nrp1) as a target of mir-9 and mir-181b. Data from the transwell migration assay and the tube-formation assay indicated that miR-9 and mir-181b inhibited the arsenic-induced EA.hy926 cell migration and tube formation by targeting NRP1. Our study demonstrates that the environmental toxin, sodium arsenite, induced angiogenesis by altering the expression of miRNAs and their cognate mRNA targets. J. Cell. Physiol. © 2011 Wiley Periodicals, Inc.