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Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice

Cited 2 time in Web of Science Cited 3 time in Scopus
Authors
Lee, Chai-Jin; Ahn, Hongryul; Lee, Sean Bong; Shin, Jong-Yeon; Park, Woong-Yang; Kim, Jong-Il; Lee, Junghee; Ryu, Hoon; Kim, Sun
Issue Date
2016-08-12
Publisher
BioMed Central
Citation
BMC Medical Genomics, 9(Suppl 1):33
Keywords
EWSEwsr1Gnai1MMIAPPINetwork analysis
Description
This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Abstract
Abstract

Background
Multifunctional transcription factor (TF) gene EWS/EWSR1 is involved in various cellular processes such as transcription regulation, noncoding RNA regulation, splicing regulation, genotoxic stress response, and cancer generation. Role of a TF gene can be effectively studied by measuring genome-wide gene expression, i.e., transcriptome, in an animal model of Ews/Ewsr1 knockout (KO). However, when a TF gene has complex multi-functions, conventional approaches such as differentially expressed genes (DEGs) analysis are not successful to characterize the role of the EWS gene. In this regard, network-based analyses that consider associations among genes are the most promising approach.


Methods
Networks are constructed and used to show associations among biological entities at various levels, thus different networks represent association at different levels. Taken together, in this paper, we report contributions on both computational and biological sides.


Results
Contribution on the computational side is to develop a novel computational framework that combines miRNA-gene network and protein-protein interaction network information to characterize the multifunctional role of EWS gene. On the biological side, we report that EWS regulates G-protein, Gnai1, in the spinal cord of Ews/Ewsr1 KO mice using the two biological network integrated analysis method. Neighbor proteins of Gnai1, G-protein complex subunits Gnb1, Gnb2 and Gnb4 were also down-regulated at their gene expression level. Interestingly, up-regulated genes, such as Rgs1 and Rgs19, are linked to the inhibition of Gnai1 activities. We further verified the altered expression of Gnai1 by qRT-PCR in Ews/Ewsr1 KO mice.


Conclusions
Our integrated analysis of miRNA-transcriptome network and PPI network combined with qRT-PCR verifies that Gnai1 function is impaired in the spinal cord of Ews/Ewsr1 KO mice.
Language
English
URI
http://hdl.handle.net/10371/100683
DOI
https://doi.org/10.1186/s12920-016-0195-4
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College of Natural Sciences (자연과학대학)Program in Bioinformatics (협동과정-생물정보학전공)Journal Papers (저널논문_협동과정-생물정보학전공)
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