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

Abstract

Recently, sperm-associated antigen 6 (<i>SPAG6</i>), a member of the cancer-testis antigen family, has been shown to be involved in tumorigenesis. An increasing number of studies have shown that <i>SPAG6</i> expression is associated with the pathogenesis of myelodysplastic syndrome (MDS). However, the mechanism has not been clearly elucidated. Our previous results indicated that <i>SPAG6</i> 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 <i>SPAG6</i> 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 <i>SPAG6</i> had poor survival. The results of the cell counting kit-8, FACS, RT-qPCR, and Western blotting assays indicated that <i>SPAG6</i> knockdown in the SKM-1 cell line inhibited cell proliferation, and affected cell cycle and differentiation. Furthermore, we found that <i>SPAG6</i> 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 <i>SPAG6</i> knockdown was associated with the upregulation of the cyclin-dependent kinase inhibitor p27Kip1, and regulation of the AKT/FOXO pathway. These findings indicated that <i>SPAG6</i> might be a potential therapeutic target.