PURPOSE Sialic acid-bound immunoglobulin-like lectin 15 (Siglec15) has emerged as a novel therapeutic target in tumor immunotherapy. This study is designed to investigate the function and mechanism of Siglec15 in thyroid carcinoma (THCA). MATERIALS AND METHODS The information on patients with THCA from TGCA and GEO database were used to analyze the expression of Siglec15 in THCA. THCA cells were treated with Siglec15-mFc, a recombinant fusion protein consisting of the extracellular domain of human Siglec15 and murine IgG Fc. THP-1 cells expressing human Siglec15 and its mutant were co-cultured with THCA cells to mimic the contact between Siglec15-expressing tumor-associated macrophages and THCA cells. Wound-healing assay and transwell migration assay were used to examine the migration abilities of BCPAP and C643 cells. Pull-down assay was performed to examine the interaction between Siglec15 and epidermal growth factor receptor (EGFR) on the cancer cells. Cycloheximide (CHX) assay was used to evaluate the stability of the protein. RESULTS The expression of Siglec15 in thyroid carcinoma tissues is higher than in normal tissues. Siglec15 promotes the migration of THCA cells by binding to EGFR in a sialic acid-dependent manner and increases EGFR protein expression. Inhibition of the EGFR pathway blocks the effect of Siglec15 on the migration of THCA cells. CONCLUSIONS Our findings reveals that Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.

中文翻译：

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Siglec15通过增强EGFR蛋白稳定性来促进甲状腺癌细胞的迁移。

目的唾液酸结合免疫球蛋白样凝集素 15 (Siglec15) 已成为肿瘤免疫治疗中的新型治疗靶点。本研究旨在探讨Siglec15在甲状腺癌（THCA）中的功能和机制。材料与方法利用TGCA和GEO数据库中的THCA患者信息，分析THCA中Siglec15的表达情况。THCA 细胞用 Siglec15-mFc 处理，Siglec15-mFc 是一种重组融合蛋白，由人 Siglec15 的胞外结构域和鼠 IgG Fc 组成。将表达人 Siglec15 及其突变体的 THP-1 细胞与 THCA 细胞共培养，以模拟表达 Siglec15 的肿瘤相关巨噬细胞与 THCA 细胞之间的接触。采用伤口愈合实验和Transwell迁移实验检测BCPAP和C643细胞的迁移能力。进行 Pull-down 测定来检查 Siglec15 和癌细胞上表皮生长因子受体 (EGFR) 之间的相互作用。放线菌酮 (CHX) 测定用于评估蛋白质的稳定性。结果 Siglec15在甲状腺癌组织中的表达高于正常组织。Siglec15通过以唾液酸依赖性方式与EGFR结合来促进THCA细胞的迁移并增加EGFR蛋白表达。抑制 EGFR 通路可阻断 Siglec15 对 THCA 细胞迁移的影响。结论我们的研究结果表明，Siglec15 通过增强 EGFR 蛋白稳定性来促进甲状腺癌细胞的迁移。放线菌酮 (CHX) 测定用于评估蛋白质的稳定性。结果 Siglec15在甲状腺癌组织中的表达高于正常组织。Siglec15通过以唾液酸依赖性方式与EGFR结合来促进THCA细胞的迁移并增加EGFR蛋白表达。抑制 EGFR 通路可阻断 Siglec15 对 THCA 细胞迁移的影响。结论我们的研究结果表明，Siglec15 通过增强 EGFR 蛋白稳定性来促进甲状腺癌细胞的迁移。放线菌酮 (CHX) 测定用于评估蛋白质的稳定性。结果 Siglec15在甲状腺癌组织中的表达高于正常组织。Siglec15通过以唾液酸依赖性方式与EGFR结合来促进THCA细胞的迁移并增加EGFR蛋白表达。抑制 EGFR 通路可阻断 Siglec15 对 THCA 细胞迁移的影响。结论我们的研究结果表明，Siglec15 通过增强 EGFR 蛋白稳定性来促进甲状腺癌细胞的迁移。抑制 EGFR 通路可阻断 Siglec15 对 THCA 细胞迁移的影响。结论我们的研究结果表明，Siglec15 通过增强 EGFR 蛋白稳定性来促进甲状腺癌细胞的迁移。抑制 EGFR 通路可阻断 Siglec15 对 THCA 细胞迁移的影响。结论我们的研究结果表明，Siglec15 通过增强 EGFR 蛋白稳定性来促进甲状腺癌细胞的迁移。