The following is a summary of “Exosome-mediated Delivery of miR-519e-5p Promotes Malignant Tumor Phenotype and CD8+ T-Cell Exhaustion in Metastatic PTC,” published in the June 2024 issue of Endocrinology by Li, et al.

In patients with papillary thyroid carcinomas (PTCs), distant metastases are the primary cause of therapy failure and mortality. However, the underlying mechanisms initiating tumor cell dissemination and metastasis in PTCs need to be better-explored. For a study, researchers sought to probe the effects and molecular mechanisms underlying circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs.

Through miRNA microarray analysis, quantitative real-time polymerase chain reaction (qRT–PCR) assays, and receiver operating characteristic (ROC) curves, the most relevant circulating exosomal miRNA in distant metastatic PTCs was identified. They further investigated the parental and recipient cells of this circulating exosomal miRNA. In vitro and in vivo experiments were conducted to elucidate the function and potential mechanisms of circulating exosomal miRNAs contributing to distant metastases.

The study revealed significant upregulation of PTC-derived exosomal miR-519e-5p in the circulatory system of distant metastatic PTCs. Subsequent experiments indicated that PTC cells could acquire a more aggressive phenotype through hnRNPA2B1-mediated sorting of tumor suppressor miR-519e-5p into exosomes, activating the Wnt signaling pathway by upregulating PLAGL2. Additionally, miR-519e-5p, encapsulated in PTC-derived exosomes, was found to transfer to recipient CD8+ T cells, facilitating tumor immune escape in distant organs by inhibiting the Notch signaling pathway via downregulation of NOTCH2.

The findings shed light on the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, offering insights into exosome-mediated mechanisms of distant metastases in PTCs.

Reference: academic.oup.com/jcem/article-abstract/109/6/1601/7468981