FXYD Domain Containing Ion Transport Regulator 3 (FXYD3) is Over-Expressed in Germinal Centre Derived Aggressive Lymphomas and Plasma Cell Myeloma

Abstract

FXYD3 is a Na/K-ATPase regulator which has been recently associated with different cancers development and progression; consequently, FXYD3 has been proposed in those as a potential therapeutic target. By contrast, no data are available concerning FXYD3 expression in hematological malignancies. In this study we aimed to assess FXYD3 gene expression in a large panel of B-cell derived lymphoid malignancies and to evaluate possible clinic-pathological correlations. Normal B-cell subsets served as control. We found that FXYD3 gene was not significantly modulated in normal B-cells. By contrast, BL, DLBCL, PMBCL, and PCM presented with a significant over-expression of the gene when compared to their cellular counterpart (p<0.0006). Interestingly, tumors characterized by higher FXYD3 expression presented with a significant enrichment in specific cellular functions and pathways, including NFkB pathway, WNT/B-catenin signaling, and MYC network, while FXYD3 levels also turned out to be directly related to PRDM1/BLIMP1. Finally, higher FXYD3 expression was not significantly associated with patients' survival in PCM and DLBCL, though a trend in favour of patients with lower expression was recorded in DLBCL cases. In conclusion, we unveiled FXYD3 gene over-expression in specific non-Hodgkin lymphoma subtypes and PCM, providing evidences of its involvement in their pathobiology. Future studies are needed to define its precise role.

Integrated Analysis of Microarray and RNA-Seq Data for the Identification of Hub Genes and Networks Involved in the Pancreatic Cancer

“…The FXYD domain containing ion transport regulator 3 (FXYD3) is the member of the small membrane proteins family. FXYD3 function as Na/K-ATPase regulator and induces a hyperpolarization-activated current in membrane by changing K+ and Na+ affinity of Na/K-ATPase (Bibert et al, 2006;Peron et al, 2019). FXYD3 is also known as mammary tumor marker 8 (Mat-8), and cell proliferation is considered as a plausible role of FXYD3 in cancer.…”