IL1β Functions as a Tumor Suppressor in Papillary Thyroid Carcinoma via the SMDT1-MAPK Signaling Axis

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. Although most patients have favorable outcomes, a subset of patients develop aggressive disease characterized by lymph node metastasis and recurrence. Increasing evidence indicates that inflammatory factors participate in tumor progression. However, the expression pattern and functional role of interleukin-1 beta (IL1β) in PTC remain unclear. This study aimed to investigate the expression, biological function, and underlying molecular mechanisms of IL1β in PTC progression. Methods: IL1β expression and its clinical relevance were evaluated using public databases, 152 paired PTC and adjacent non-cancerous tissue samples, and PTC cell lines. Functional assays, including cell proliferation, colony formation, wound-healing, transwell invasion, and flow cytometry assays, were performed to investigate the effects of IL1β on malignant phenotypes. RNA sequencing, proteomic analysis, co-immunoprecipitation assays, rescue experiments, and a xenograft mouse model were conducted to identify and validate the downstream molecular mechanisms of IL1β. Results: IL1β expression was significantly reduced in PTC tissues and cell lines and was negatively associated with lymph node metastasis. Overexpression or recombinant protein treatment of IL1β inhibited PTC cell proliferation, migration, invasion, epithelial–mesenchymal transition, and tumor growth, while promoting apoptosis. Mechanistically, IL1β increased the expression of SMDT1 gene and suppressed MAPK signaling activity by reducing MEK/ERK phosphorylation. Knockdown of SMDT1 gene partially reversed the inhibitory effects of IL1β on PTC cell progression and MAPK pathway activation. Conclusions: This study demonstrates that IL1β functions as a tumor suppressor in PTC through regulation of the SMDT1-MAPK signaling axis. These findings provide new insights into the role of inflammatory regulation in thyroid cancer (THCA) progression and suggest that IL1β-related molecular pathways may represent potential biomarkers or therapeutic targets for aggressive PTC.