1st International and 10th National Iranian Conference on Bioinformatics
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A systems biology approach shows that RUNX1 can be considered as a potential target to inhibit glioblastoma progression
Paper ID : 1174-ICB10
Authors:
شراره محمودیان-همدانی1, Parvaneh Nikpour *2
1گروه ژنتیک و بیولوژی مولکولی-دانشکده پزشکی-دانشگاه علوم پزشکی اصفهان
2Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract:
Background: Glioblastoma is the most common brain tumor with a 5 year-survival rate of about 5% which puts it among the most life-threatening cancers [1]. One of the notable genes that has been the center of focus in many cancer studies, specially in those related to aggressive solid tumors, is RUNX1. It has been found that RUNX1 has a dual role in cancer progression, meaning that in some cancers promotes the proliferation and progression while in some others acts as a tumor suppressor [2]. In the following study, using gene expression profiles from Gene Expression Omnibus (GEO) database and a systems biology approach, we tried to examine the role of RUNX1 in the glioblastoma A172 cell line.

Materials and Methods: Gene expression data from GEO (GSE174634) including six samples of A172 glioblastoma cell line, in three of which RUNX1 expression is suppressed, was firstly downloaded. Differentially expressed genes were then extracted using GEO2R tool with adjusted p-value <0.05 and a network was constructed using Cytoscape. Functional enrichment analysis was performed using CluePedia plug-in. MCODE was used to screen the modules of the network.

Results: 220 genes were shown to be differentially-expressed between RUNX1- and RUNX1+ samples. A network was then constructed with 166 nodes and 568 edges. By using MCODE plug-in, four clusters were identified in the network. Reactome pathway analysis for 166 nodes showed that highly enriched pathways in the network are related to condensation of pro-metaphase chromosomes, G1/S transition, cell cycle and transcriptional regulation of TP53. The results of KEGG functional enrichment analysis demonstrated that selected genes are highly involve in p53 signaling pathway, cell cycle and FOXO signaling pathway.

Conclusion: This study showed that RUNX1 knock-down results in upregulation of pathways related to tumor suppression, and RUNX1 can be considered as a potential target for glioblastoma treatment.
Keywords:
Key words: Glioblastoma, RUNX1, Systems biology, Cytoscape, Gene expression network
Status : Paper Accepted (Poster Presentation)