Document Type : Original Article
Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
Department of Medical Immunology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
Introduction:The present study attempted to investigate the key pathways and genes which are associated with hypoxia in the human breast carcinoma cell line MDA-MB-231 with searched in gene expression omnibus (GEO) database for mRNA microarray data of MDA-MB-231 in normal and hypoxia condition.
Methods: Three GEO datasets GSE37340, GSE39042, and GSE42416 were downloaded from the Gene Expression Omnibus (GEO) database that these GEO profiles have of 9 cell lines in hypoxia condition and eight cell lines in normal condition. The differentially expressed genes (DEGs) between MDA-MB-231 cell line in hypoxia and normal condition were analyzed by Geo2R software. Next, all the differentially expressed genes (DEGs) with p<0.05 and fold change ≥1 or ≤-1 was identified. Among all the differentially expressed genes, only 32 genes were at least in two datasets (31 up regulated and 1 down regulated) after gene integration. Moreover, DEGs ontology terms, Kyoto Encyclopedia and Genomes pathways were analyzed using EnrichR database. Subsequently, a protein-protein interaction network was constructed using STRING and MCODE software. Finally, the survival analyses performed with Kaplan Meier-plotter (KM) online dataset.
Results: Thirty-two genes were found to be at least two datasets (i.e., SLC2A3, BNIP3, ENO2, PFKFB3, PLOD2, SLC2A1, HK2, ADM, etc.) that two genes among up regulated genes (HK2, ADM) were expressed in all three datasets.
Conclusion: These identified genes and pathways could help to understand the mechanism of development of (Triple-negative breast cancer) TNBC under hypoxia condition. Also HK2, ADM, CENP family, might be promising targets for the TNBC treatment.