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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis
BMC Genomics, Volume 14, No. 1, Article 23, Year 2013
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Description
Background: Apoptosis is a critical process in endothelial cell (EC) biology and pathology, which has been extensively studied at protein level. Numerous gene expression studies of EC apoptosis have also been performed, however few attempts have been made to use gene expression data to identify the molecular relationships and master regulators that underlie EC apoptosis. Therefore, we sought to understand these relationships by generating a Bayesian gene regulatory network (GRN) model.Results: ECs were induced to undergo apoptosis using serum withdrawal and followed over a time course in triplicate, using microarrays. When generating the GRN, this EC time course data was supplemented by a library of microarray data from EC treated with siRNAs targeting over 350 signalling molecules.The GRN model proposed Vasohibin-1 (VASH1) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by VASH1 in EC, we used siRNA to reduce the expression of VASH1. Of 10 mRNAs downstream of VASH1 in the GRN that were examined, 7 were significantly up- or down-regulated in the direction predicted by the GRN.Further supporting an important biological role of VASH1 in EC, targeted reduction of VASH1 mRNA abundance conferred resistance to serum withdrawal-induced EC death. Conclusion: We have utilised Bayesian GRN modelling to identify a novel candidate master regulator of EC apoptosis. This study demonstrates how GRN technology can complement traditional methods to hypothesise the regulatory relationships that underlie important biological processes. © 2013 Affara et al.; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3570387/bin/1471-2164-14-23-S1.xml
https://efashare.b-cdn.net/share/pmc/articles/PMC3570387/bin/1471-2164-14-23-S2.txt
https://efashare.b-cdn.net/share/pmc/articles/PMC3570387/bin/1471-2164-14-23-S3.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3570387/bin/1471-2164-14-23-S4.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3570387/bin/1471-2164-14-23-S5.xlsx
Authors & Co-Authors
Affara, Muna
United Kingdom, Cambridge
University of Cambridge
Sanders, Debbie
United Kingdom, Cambridge
University of Cambridge
Araki, Hiromitsu
Japan, Fukuoka
Gni Ltd.
Tamada, Yoshinori
Japan, Tokyo
The University of Tokyo
Dunmore, Benjamin J.
United Kingdom, Cambridge
University of Cambridge
Humphreys, Sally
United Kingdom, Cambridge
University of Cambridge
Imoto, Seiya
Japan, Tokyo
The University of Tokyo
Savoie, Christopher
Japan, Fukuoka
Gni Ltd.
Miyano, Satoru
Japan, Tokyo
The University of Tokyo
Kuhara, Satoru
Japan, Fukuoka
Kyushu University
Jeffries, David J.
Gambia
Mrc
Print, Cristin
New Zealand, Auckland
The University of Auckland
Charnock-Jones, D. Stephen
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Birmingham
National Institute for Health Research
Statistics
Citations: 13
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1186/1471-2164-14-23
e-ISSN:
14712164
Research Areas
Cancer
Genetics And Genomics