Overexpression of <scp>FMOD</scp> in Thyroid Carcinoma Triggers <scp>M1</scp> ‐Like Tumor‐Associated Macrophage Polarization by Targeting <scp>Rap1B</scp>

Thyroid carcinoma, with limited efficacy of current treatment, influences the lives and health of many people. It is important to explore potential therapeutic targets for thyroid carcinoma. Fibromodulin (FMOD) has been indicated to be connected with the progression of different kinds of tumors, with unknown functions in thyroid carcinoma. In this study, the potential candidate therapeutic targets for thyroid carcinoma were identified by bioinformatics methods, and FMOD was screened out for verification. Cell counting kit-8, wound healing, transwell, and flow cytometry assays were conducted to determine the role of FMOD overexpression in cell viability, migration, invasion, and apoptotic rate of thyroid carcinoma cells, respectively. Subcutaneous tumor growth was monitored in nude mice. Tumor-associated macrophages (TAMs) were co-cultured with thyroid carcinoma cells, and the surface marker of M1-like TAMs, CD80, was identified by flow cytometry. Ras-association proximate 1B (Rap1B), the downstream target of FMOD, was predicted by bioinformatic techniques and validated by Rap1B overexpression rescue. FMOD was identified as a tumor suppressor gene in thyroid carcinoma through bioinformatic techniques. FMOD overexpression inhibited cell viability, migration, and invasion and stimulated apoptosis of thyroid carcinoma cells. In vivo, FMOD upregulation could suppress the growth of solid tumors. Moreover, FMOD overexpression in thyroid carcinoma cells promoted M1-like TAM polarization. FMOD downregulated Rap1B expression in thyroid carcinoma cells, and Rap1B overexpression rescue reversed the impact of FMOD on tumor progression and TAM polarization. In conclusion, FMOD exhibited an inhibitory effect on thyroid carcinoma by stimulating M1-like TAM polarization via targeting Rap1B.