Differentially Expressed Genes Induced by Erythropoietin Receptor Overexpression in Rat Mammary Adenocarcinoma RAMA 37-28 Cells

The erythropoietin receptor (EPOR) is a transmembrane type I receptor with an essential role in the proliferation and differentiation of erythroid progenitors. Besides its function during erythropoiesis, EPOR is expressed and has protective effect in various non-hematopoietic tissues, including tumors. Currently, the advantageous aspect of EPOR related to different cellular events is still under scientific investigation. Besides its well-known effect on cell proliferation, apoptosis and differentiation, our integrative functional study revealed its possible associations with metabolic processes, transport of small molecules, signal transduction and tumorigenesis. Comparative transcriptome analysis (RNA-seq) identified 233 differentially expressed genes (DEGs) in EPOR overexpressed RAMA 37-28 cells compared to parental RAMA 37 cells, whereas 145 genes were downregulated and 88 upregulated. Of these, for example, GPC4, RAP2C, STK26, ZFP955A, KIT, GAS6, PTPRF and CXCR4 were downregulated and CDH13, NR0B1, OCM2, GPM6B, TM7SF3, PARVB, VEGFD and STAT5A were upregulated. Surprisingly, two ephrin receptors, EPHA4 and EPHB3, and EFNB1 ligand were found to be upregulated as well. Our study is the first demonstrating robust differentially expressed genes evoked by simple EPOR overexpression without the addition of erythropoietin ligand in a manner which remains to be elucidated.

Automated summary

The erythropoietin receptor (EPOR) plays an essential role in the proliferation and differentiation of erythroid progenitors, and it also has a protective effect in non-hematopoietic tissues including tumors. In addition to its well-known function in cell proliferation, apoptosis, and differentiation, EPOR is also associated with metabolic processes, small molecule transport, signal transduction, and tumorigenesis. Through comparative transcriptome analysis, 233 differentially expressed genes were identified in cells overexpressing EPOR, including downregulated genes such as GPC4, RAP2C, STK26, and upregulated genes such as CDH13, NR0B1, OCM2. Surprisingly, ephrin receptors EPHA4 and EPHB3, as well as EFNB1 ligand, were also found to be upregulated.