A systems biology approach shows that RUNX۱ can be considered as a potential target to inhibit glioblastoma progression

Background: Glioblastoma is the most common brain tumor with a ۵ year-survival rate of about ۵% whichputs it among the most life-threatening cancers. One of the notable genes that has been the center of focus inmany cancer studies, specially in those related to aggressive solid tumors, is RUNX۱. It has been found thatRUNX۱ has a dual role in cancer progression, meaning that in some cancers promotes the proliferation andprogression while in some others acts as a tumor suppressor. In the following study, using gene expressionprofiles from Gene Expression Omnibus (GEO) database and a systems biology approach, we tried toexamine the role of RUNX۱ in the glioblastoma A۱۷۲ cell line.Materials and Methods: Gene expression data from GEO (GSE۱۷۴۶۳۴) including six samples of A۱۷۲glioblastoma cell line, in three of which RUNX۱ expression is suppressed, was firstly downloaded.Differentially expressed genes were then extracted using GEO۲R tool with adjusted p-value <۰.۰۵ and anetwork was constructed using Cytoscape. Functional enrichment analysis was performed using CluePediaplug-in. MCODE was used to screen the modules of the network.Results: ۲۲۰ genes were shown to be differentially-expressed between RUNX۱- and RUNX۱+ samples. Anetwork was then constructed with ۱۶۶ nodes and ۵۶۸ edges. By using MCODE plug-in, four clusters wereidentified in the network. Reactome pathway analysis for ۱۶۶ nodes showed that highly enriched pathwaysin the network are related to condensation of pro-metaphase chromosomes, G۱/S transition, cell cycle andtranscriptional regulation of TP۵۳. The results of KEGG functional enrichment analysis demonstrated thatselected genes are highly involve in p۵۳ signaling pathway, cell cycle and FOXO signaling pathway.Conclusion: This study showed that RUNX۱ knock-down results in upregulation of pathways related totumor suppression, and RUNX۱ can be considered as a potential target for glioblastoma treatment.

Keywords:

Glioblastoma , RUNX۱ , Systems biology , Cytoscape , Gene expression network