SEMA6B promotes thyroid tumorigenesis and chemoresistance via WNT/β-catenin signaling in response to doxorubicin.

Abstract

Thyroid cancer (THCA) is the most common endocrine malignancy and typically has a favorable prognosis. However, aggressive subtypes, particularly anaplastic thyroid carcinoma, present significant treatment challenges due to their high metastatic potential and resistance to conventional therapies. Therefore, a better understanding of the underlying mechanisms is essential for improving treatment strategies. Herein, we aimed to investigate the role of SEMA6B in THCA progression and explore its associated molecular mechanisms. Differentially expressed genes (DEGs) in THCA was screened using RNA sequencing data from paired THCA and normal tissues of 10 patients. The expression and functional role of SEMA6B in THCA were further examined using datasets from TCGA and GEO. Functional assays were conducted to evaluate the effects of SEMA6B overexpression and knockout on THCA cell proliferation. In vivo xenograft assays were performed to validate these findings. Additionally, the impact of SEMA6B on the WNT/β-catenin signaling pathway was verified. SEMA6B was highly expressed in THCA and significantly associated with poor clinical outcomes. SEMA6B overexpression significantly increased cell proliferation and colony formation, whereas its knockout reduced cell proliferation and enhanced sensitivity to Doxorubicin. Mechanistically, SEMA6B was found to promote activation of the WNT/β-catenin signaling pathway. In conclusion, these data reveal a novel oncogenic role for the SEMA6B/WNT/β-catenin signaling pathway in THCA, providing new insights and potential avenues for therapeutic intervention.