@Article{or.2025.067182,
AUTHOR = {Yan Gui, Wen Pan, Ziyi Dong, Dongzhi Hu, Yaoyang Guo, Xinyi Wen, Haiyang Zhang, Zhansheng Jiang, Xiangqian Zheng, Ming Gao, Junyi Wang},
TITLE = {Exosomal miR-17 Drives Thyroid Cancer Lung Metastasis via NF-<b>κ</b>B Activation},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {12},
PAGES = {3991--4011},
URL = {http://www.techscience.com/or/v33n12/64624},
ISSN = {1555-3906},
ABSTRACT = { <b>Objectives:</b> Metastatic spread to the lung is one of the leading causes of fatal outcomes in thyroid cancer, but the underlying molecular mechanisms remain unclear. To investigate how exosomal microRNA-17-5p (miR-17-5p) promotes lung metastasis in thyroid cancer within the framework of the “seed and soil” hypothesis. <b>Methods:</b> Serum exosomes from thyroid cancer lung metastasis patients and controls were analyzed for miR-17, which was elevated in metastatic cases. miR-17 was transfected into embryonic lung fibroblasts (MRC-5), and their supernatants were co-cultured with thyroid cancer cells (Cal62). Cell proliferation and migration were evaluated using colony formation, Ki67 staining, and Transwell assays. Interleukin-6 (IL-6)/interleukin-8 (IL-8) levels and nuclear factor kappa-B (NF-κB)/nuclear factor kappa-B repressing factor (NKRF) expression were analysed by enzyme-linked immunosorbent assays (ELISA) and western blot. <i>In vivo</i> models verified the metastatic-promoting effect of miR-17. <b>Results:</b> miR-17-5p was significantly enriched in serum exosomes of metastatic patients. In MRC-5 cells, it suppressed NKRF, NF-κB signaling, and increased secretion of IL-6 and IL-8, enhancing Cal62 proliferation and migration. Animal experiments confirmed its role in promoting tumor growth and lung metastasis. <b>Conclusions:</b> Exosomal miR-17-5p remodels the pulmonary microenvironment into a pro-inflammatory niche, facilitating thyroid cancer colonization and offering a potential therapeutic target.},
DOI = {10.32604/or.2025.067182}
}