1. Exosome-mediated Delivery of miR-519e-5p Promotes Malignant Tumor Phenotype and CD8+ T-Cell Exhaustion in Metastatic PTC.
- Author
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Li G, Chen W, Jiang K, Huang J, Zhong J, Liu X, Wei T, Gong R, Li Z, Zhu J, Shi H, and Lei J
- Subjects
- Humans, Animals, Mice, Gene Expression Regulation, Neoplastic, Neoplasm Metastasis, Phenotype, Male, Cell Line, Tumor, Female, Middle Aged, Mice, Nude, T-Cell Exhaustion, MicroRNAs genetics, Exosomes metabolism, Exosomes genetics, CD8-Positive T-Lymphocytes metabolism, Thyroid Cancer, Papillary genetics, Thyroid Cancer, Papillary pathology, Thyroid Cancer, Papillary metabolism, Thyroid Cancer, Papillary immunology, Thyroid Neoplasms pathology, Thyroid Neoplasms genetics, Thyroid Neoplasms metabolism, Thyroid Neoplasms immunology
- Abstract
Context: Distant metastases are the primary cause of therapy failure and mortality in patients with papillary thyroid carcinomas (PTCs). However, the underlying mechanism responsible for the initiation of tumor cell dissemination and metastasis in PTCs has rarely been investigated., Objective: The aim of this study was to investigate effects and underlying molecular mechanisms of circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs., Methods: The most relevant circulating exosomal miRNA to distant metastatic PTCs were verified between distant metastatic PTCs and nondistant metastatic PTCs by miRNA microarray, quantitative real-time polymerase chain reaction (qRT-PCR) assays and receiver operating characteristic (ROC) curves. The parental and recipient cells of that circulating exosomal miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of circulating exosomal miRNAs that contribute to the development of distant metastases., Results: We determined that PTC-derived exosomal miR-519e-5p was significantly upregulated in the circulatory system in distant metastatic PTCs. Further tests demonstrated that PTC cells can acquire a more malignant phenotype via hnRNPA2B1-mediated sorting of tumor suppressor miR-519e-5p into exosomes to activate Wnt signaling pathway via upregulating PLAGL2. Furthermore, miR-519e-5p included in PTC-derived exosomes can be transferred to recipient CD8+ T cells and aid in tumor immune escape in distant organs through inhibiting Notch signaling pathway by downregulating NOTCH2., Conclusion: Our findings highlight the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, which may improve our understanding of exosome-mediated distant metastatic mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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