Association between DPAGT1 and Siglec-15 expression and the malignant phenotype of hepatocellular carcinoma

N-acetylglucosamine phosphotransferase 1 (DPAGT1), a key enzyme involved in protein glycosylation, has been implicated in tumor progression; however, its relationship with sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) in hepatocellular carcinoma (HCC) remains unclear. This study investigated the association between DPAGT1 expression, Siglec-15 expression, and malignant phenotypes in HCC. Bioinformatic analysis of the GEPIA database revealed higher expression of DPAGT1 and Siglec-15 in HCC tissues. Higher DPAGT1 expression was associated with poorer overall survival, whereas Siglec-15 expression showed no significant association with survival outcomes. Although DPAGT1 and Siglec-15 expression levels showed a statistically significant correlation, the correlation strength was weak. Functional experiments demonstrated that DPAGT1 overexpression promoted proliferation, migration, and invasion of HCC cells, whereas DPAGT1 knockdown resulted in reduced malignant phenotypes. Re-expression of Siglec-15 partially alleviated the inhibitory effects associated with DPAGT1 depletion. Similar alterations were observed in Hep-3B cells and a xenograft model, where DPAGT1 modulation was associated with changes in tumor growth, Siglec-15 expression, TGF-β1 levels, AKT phosphorylation, and EMT-related molecular markers. Collectively, these findings suggest that DPAGT1 may contribute to HCC progression and is functionally associated with Siglec-15 expression and EMT-related molecular alterations. Further studies are required to clarify the underlying molecular relationship between DPAGT1 and Siglec-15.