Siglec15 as a potential therapeutic target for the treatment of fibrosarcoma.

e23552 Background: Traditional therapeutic approaches, including surgery, radiotherapy, and chemotherapy, have limited effectiveness in controlling the progression of fibrosarcoma. The development of new therapeutic targets is of great significance for improving the prognosis of fibrosarcoma. Our previous studies have found that the high expression of Siglec15 at both the gene and protein levels is negatively correlated with the clinical prognosis of fibrosarcoma. Methods: First, the high expression of Siglec15 at both the gene and protein levels was verified in wild-type human HT-1080 and mouse WEHI164 fibrosarcoma cell lines. Subsequently, Siglec15 gene knockdown HT-1080 and WEHI164 cell lines, as well as stable transgenic lines transfected with lentivirus, were constructed. The effects of Siglec15 knockdown on tumor cell proliferation, apoptosis, cell cycle progression, and invasion were investigated using CCK8, TUNEL staining, and flow cytometry analysis. Additionally, the role of Siglec15 in tumor progression was explored using a mouse orthotopic fibrosarcoma model. Results: After Siglec15 knockdown, tumor cell proliferation, anti-apoptotic and invasion capacity were significantly reduced, and G0/G1 phase arrest was notably improved. In the mouse orthotopic tumor model, Siglec15 knockdown significantly slowed tumor growth and increased treatment sensitivity to X-ray and chemotherapeutic drugs (model drug DOX). Conclusions: These findings suggest that Siglec15 is an emerging therapeutic target with significant potential for the treatment of fibrosarcoma.