TY - JOUR
T1 - 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
AU - Lee, Chai Jin
AU - Ahn, Hongryul
AU - Lee, Sean Bong
AU - Shin, Jong Yeon
AU - Park, Woong Yang
AU - Kim, Jong Il
AU - Lee, Junghee
AU - Ryu, Hoon
AU - Kim, Sun
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/8/12
Y1 - 2016/8/12
N2 - 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.
AB - 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.
KW - EWS
KW - Ewsr1
KW - Gnai1
KW - MMIA
KW - Network analysis
KW - PPI
UR - https://www.scopus.com/pages/publications/84982187968
U2 - 10.1186/s12920-016-0195-4
DO - 10.1186/s12920-016-0195-4
M3 - Article
C2 - 27534535
AN - SCOPUS:84982187968
SN - 1755-8794
VL - 9
JO - BMC Medical Genomics
JF - BMC Medical Genomics
M1 - 33
ER -
