Upregulation of SPAG6 in Myelodysplastic Syndrome: Knockdown Inhibits Cell Proliferation via AKT/FOXO Signaling Pathway

Abstract

Recently, sperm-associated antigen 6 (SPAG6), a member of the cancer-testis antigen family, has been shown to be involved in tumorigenesis. An increasing number of studies have shown that SPAG6 expression is associated with the pathogenesis of myelodysplastic syndrome (MDS). However, the mechanism has not been clearly elucidated. Our previous results indicated that SPAG6 affected cell apoptosis in MDS. In this study, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to demonstrate that the mRNA expression of SPAG6 in bone marrow cells of patients with MDS or MDS-derived acute myeloid leukemia (MDS-AML) was higher than that of cancer-free patients. Kaplan-Meier survival curve analysis of published AML found that patients with high expression of SPAG6 had poor survival. The results of the cell counting kit-8, FACS, RT-qPCR, and Western blotting assays indicated that SPAG6 knockdown in the SKM-1 cell line inhibited cell proliferation, and affected cell cycle and differentiation. Furthermore, we found that SPAG6 knockdown affected the proliferation of SKM-1 cells by mediating the G1-to-S transition of the cell cycle. Moreover, we demonstrated that the antiproliferative effect of SPAG6 knockdown was associated with the upregulation of the cyclin-dependent kinase inhibitor p27Kip1, and regulation of the AKT/FOXO pathway. These findings indicated that SPAG6 might be a potential therapeutic target.

Keywords: AKT/FOXO; SPAG6; cell proliferation; myelodysplastic syndrome; p27Kip1.