Retinoid X receptor γ regulates epithelial-mesenchymal transition and tumor immune infiltration in papillary thyroid cancer tumorigenesis: an experimental and in silico study.
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引用次数: 0
Abstract
Objective: This study aimed to elucidate the functional role and underlying molecular mechanisms of retinoid X receptor γ (RXRG) in the pathogenesis of papillary thyroid carcinoma (PTC).
Methods: We analyzed RNA-seq data from The Cancer Genome Atlas database, ONCOMINE database, and Human Protein Atlas. RXRG expression was validated in 47 matched PTC-normal tissue pairs using real-time reverse transcription-polymerase chain reaction. Functional characterization was performed through loss- and gain-of-function experiments, complemented by flow cytometry analysis. Bioinformatics approaches were employed to investigate RXRG's role in tumor immune infiltration.
Results: RXRG was significantly upregulated in PTC (P < 0.001). Elevated RXRG expression correlated with aggressive clinicopathological features, including lymph node metastasis (P = 0.041), advanced tumor stage (P = 0.035), BRAFV600E mutation (P < 0.001), and increase in tumor size (P = 0.011). Functional assays revealed that RXRG knockdown suppressed cell proliferation, colony formation, and migration capacity, whereas its overexpression promoted these oncogenic phenotypes. Mechanistically, RXRG regulated epithelial-mesenchymal transition (EMT) through modulation of E-cadherin, N-cadherin, vimentin, and key transcription factors (Snail and Slug). Furthermore, RXRG expression considerably influenced tumor immune infiltration patterns, particularly affecting eosinophils, NK cells, and B cells.
Conclusion: Our study identifies RXRG as a novel oncogenic driver in PTC that promotes tumor progression through EMT regulation and immune microenvironment modulation.
期刊介绍:
Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.