Open Access

ARTICLE

Exosomal miR-17 Drives Thyroid Cancer Lung Metastasis via NF-κB Activation

Yan Gui^1,#, Wen Pan^1,#, Ziyi Dong^1,#, Dongzhi Hu^1,#, Yaoyang Guo¹, Xinyi Wen¹, Haiyang Zhang², Zhansheng Jiang^1,*, Xiangqian Zheng^1,*, Ming Gao^2,*, Junyi Wang^1,*

1 The First Hospital of Lanzhou University, The First School of Clinical Medicine, Lanzhou University, Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Medical University Cancer Institute and Hospital, Lanzhou, 730030, China
2 Tianjin Institute of Coloproctology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China

* Corresponding Authors: Zhansheng Jiang. Email: ; Xiangqian Zheng. Email: ; Ming Gao. Email: ; Junyi Wang. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2025, 33(12), 3991-4011. https://doi.org/10.32604/or.2025.067182

Received 26 April 2025; Accepted 09 September 2025; Issue published 27 November 2025

Abstract

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.

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