Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis

Muna Affara, Debbie Sanders, Hiromitsu Araki, Yoshinori Tamada, Benjamin J. Dunmore, Sally Humphreys, Seiya Imoto, Christopher Savoie, Satoru Miyano, Satoru Kuhara, David Jeffries, Cristin Print, D. Stephen Charnock-Jones

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number23
JournalBMC Genomics
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 16 2013
Externally publishedYes

Fingerprint

Gene Regulatory Networks
Endothelial Cells
Apoptosis
Messenger RNA
Biological Phenomena
Gene Expression
Serum
Small Interfering RNA
Libraries
Cell Biology
Cell Death
Pathology
Technology

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

Cite this

Affara, M., Sanders, D., Araki, H., Tamada, Y., Dunmore, B. J., Humphreys, S., ... Charnock-Jones, D. S. (2013). Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis. BMC Genomics, 14(1), [23]. https://doi.org/10.1186/1471-2164-14-23

Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis. / Affara, Muna; Sanders, Debbie; Araki, Hiromitsu; Tamada, Yoshinori; Dunmore, Benjamin J.; Humphreys, Sally; Imoto, Seiya; Savoie, Christopher; Miyano, Satoru; Kuhara, Satoru; Jeffries, David; Print, Cristin; Charnock-Jones, D. Stephen.

In: BMC Genomics, Vol. 14, No. 1, 23, 16.01.2013.

Research output: Contribution to journalArticle

Affara, M, Sanders, D, Araki, H, Tamada, Y, Dunmore, BJ, Humphreys, S, Imoto, S, Savoie, C, Miyano, S, Kuhara, S, Jeffries, D, Print, C & Charnock-Jones, DS 2013, 'Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis', BMC Genomics, vol. 14, no. 1, 23. https://doi.org/10.1186/1471-2164-14-23
Affara, Muna ; Sanders, Debbie ; Araki, Hiromitsu ; Tamada, Yoshinori ; Dunmore, Benjamin J. ; Humphreys, Sally ; Imoto, Seiya ; Savoie, Christopher ; Miyano, Satoru ; Kuhara, Satoru ; Jeffries, David ; Print, Cristin ; Charnock-Jones, D. Stephen. / Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis. In: BMC Genomics. 2013 ; Vol. 14, No. 1.
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