Sialidase NEU3 silencing inhibits angiogenesis of EA.hy926 cells by regulating Wnt/β-catenin signaling pathway

Angiogenesis significantly drives tumor progression, and the functions of vascular endothelial cells are influenced by various factors. Tumor cells are characterized by abnormal sialylation, and their dynamic balance depends on sialyltransferases and sialidases. NEU3 is a plasma membrane-associated sialidase, vital for the regulation of cell surface sialylation. Our study revealed that, NEU3 is the most abundantly expressed among the four sialidase subtypes in EA.hy926 cells. Silencing NEU3 expression resulted in cell apoptosis and reduced proliferation, highlighting its crucial function in the regulation of cell activity. Subsequent experiments using transwell and tube formation assays demonstrated that the inhibition of NEU3 expression suppressed cell migration and angiogenesis. RNA sequencing analysis further elucidated that altering NEU3 expression in EA.hy926 cells impacts the Wnt/β-Catenin signaling pathway and c-Myc levels, thereby modulating cellular survival and migration capacity and exerting a regulatory effect on angiogenesis. These findings suggest that targeting NEU3 in the vascular endothelium may represent a promising strategy for anti-angiogenic therapy in tumors.