Abstract

Papillary thyroid carcinoma (PTC) lacks reliable molecular biomarkers and effective therapeutic targets. In this study, we investigated whether Signal Transducer and Activator of Transcription 1 (STAT1) promote PTC progression through regulation of tectonic family member 3 (TCTN3). Integrated analyses of TCGA and external datasets identified TCTN3 as a candidate oncogenic factor. Its expression was validated in paired PTC tissues and cell lines using RT-qPCR and western blotting. Functional assays, including CCK-8, EdU incorporation, colony formation, flow cytometric cell-cycle analysis, and Transwell migration/invasion assays, were performed following gain and loss of function of STAT1 and TCTN3. In vivo tumorigenicity was evaluated using nude mouse xenograft models and H&E. TCTN3 was consistently upregulated in PTC and enriched in cell-cycle related pathways. TCTN3 silencing suppressed proliferation, S-phase entry, migration, invasion, and tumor growth, whereas overexpression exerted opposite effects, accompanied by changes in PCNA, Cyclin D1, CDK4/6, MMP2, MMP9, and E-cadherin. STAT1 expression positively correlated with TCTN3 levels and modulated its expression. Chromatin immunoprecipitation and luciferase reporter assays demonstrated direct binding of STAT1 to the TCTN3 promoter, while co-immunoprecipitation confirmed the absence of direct protein interaction. STAT1 depletion phenocopied TCTN3 knockdown, and re-expression of TCTN3 rescued STAT1-deficient phenotypes. Our findings identify a STAT1-TCTN3 regulatory axis that drives cell-cycle progression, migration, and tumor growth in PTC, establishing this pathway as a mechanistically defined contributor to disease progression and a potential therapeutic target.