XPR1 Promotes the Malignant Phenotypes of Thyroid Carcinoma Cells Partly Through NF-κB-Related Signaling

Background: Xenotropic and polytropic retrovirus receptor 1 (XPR1) is highly expressed in human thyroid carcinoma (TC), yet its functional role remains unclear. In this study, we sought to determine whether XPR1 participates in the progression of thyroid carcinoma and to further uncover the molecular pathways associated with its function.Methods: XPR1 expression in thyroid carcinoma tissues was analyzed using public databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the Human Protein Atlas (HPA). XPR1 expression in thyroid carcinoma cell lines was further validated by quantitative real-time PCR (qRT-PCR) and Western blotting. Following siRNA-mediated silencing of XPR1, cell proliferative activity, clonogenic potential, and migration and invasion abilities were systematically assessed through Cell Counting Kit-8 (CCK-8) assays, clonogenic analyses, and Transwell-based experiments. Apoptotic events and the activation status of nuclear factor kappa-B (NF-κB) signaling were determined through flow cytometric analysis in combination with immunoblotting assays. Rescue experiments were performed by overexpression of p65 cDNA to restore NF-κB signaling activity.Results: Integrated analyses of GEO, TCGA, GEPIA2, and HPA datasets revealed elevated XPR1 expression in thyroid carcinoma tissues, which was further validated in thyroid carcinoma cell lines by qRT-PCR and Western blotting. Silencing XPR1 markedly suppressed the proliferative capacity, clonogenic growth, migratory and invasive abilities of thyroid carcinoma cells, while simultaneously enhancing apoptotic activity (p < 0.01). XPR1 depletion was associated with reduced p65 phosphorylation and altered expression of the apoptosis-related proteins B-cell lymphoma 2 (BCL-2) and Bax (p < 0.05). Overexpression of p65 partially reversed these changes and attenuated the inhibitory effects of XPR1 silencing (p < 0.05).Conclusion: Our results suggest that the pro-tumorigenic effects of XPR1 in thyroid carcinoma cells, manifested by increased cell growth, motility, invasiveness, and reduced susceptibility to apoptosis, may be partly associated with NF-κB signaling. Taken together, these findings suggest that XPR1 is involved in the malignant progression of thyroid carcinoma and may represent a potential molecular target worth further investigation.