TY - EJOU
AU - Gui, Yan
AU - Pan, Wen
AU - Dong, Ziyi
AU - Hu, Dongzhi
AU - Guo, Yaoyang
AU - Wen, Xinyi
AU - Zhang, Haiyang
AU - Jiang, Zhansheng
AU - Zheng, Xiangqian
AU - Gao, Ming
AU - Wang, Junyi
TI - Exosomal miR-17 Drives Thyroid Cancer Lung Metastasis via NF-κB Activation
T2 - Oncology Research
PY - 2025
VL - 33
IS - 12
SN - 1555-3906
AB - Objectives: 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. Methods: 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. In vivo models verified the metastatic-promoting effect of miR-17. Results: 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. Conclusions: Exosomal miR-17-5p remodels the pulmonary microenvironment into a pro-inflammatory niche, facilitating thyroid cancer colonization and offering a potential therapeutic target.
KW - Thyroid cancer; exosomes; microRNA-17; inflammatory environment; tumor metastasis
DO - 10.32604/or.2025.067182