TfR1 extensively regulates the expression of genes associated with ion transport and immunity

The transferrin receptor 1 (TfR1), encoded by TFRC gene, is the gatekeeper of cellular iron uptake for cells. A variety of molecular mechanisms are at work to tightly regulate TfR1 expression, and abnormal TfR1 expression was associated with diseases. In the current study, to figure out the regulation pattern of TfR1, we cloned and overexpressed human TFRC gene in HeLa cells. RNA-sequencing (RNA-seq) was used to analyze the global transcript level on overexpression-treated (OE) and normal control (NC) cell samples. 1669 differentially expressed genes (DEGs) were identified between OE and NC, and Gene ontology (GO) analysis for DEGs were carried out. It was found that lots of DEGs were associated with ion transmembrane transport and immunity. Moreover, the network was constructed on basis of DEGs regulating ion transport and immunity, the results revealed that TFRC was the node gene of the network, further suggesting that precisely controlled TfR1 expression might be not only essential for iron homeostasis, but also globally important for cell physiology, including ion transport and immunity. Overall design: To explore the regulation pattern of TfR1, we cloned and overexpressed human TFRC in HeLa cells. Subsequently, RNA-sequencing (RNA-seq) was carried out in overexpression-treated (OE) and normal control (NC) cell samples, and the results indicated that TfR1-overexpression globally affect expression levels of numerous genes. A large number of differentially expressed genes (DEGs) were identified, and Gene ontology (GO) analysis revealed that these DEGs were associated with regulation of ion transmembrane transport, immunity and transcription, suggesting abnormal high expression level of TfR1 might globally disrupt the cell physiology through molecular mechanisms.