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The cluster of microRNAs 371\u2013373 is highly upregulated in TGCTs, and detection of miR-371a-3p specifically is currently being developed for clinical implementation as a sensitive and specific biomarker for TGCT, except for teratoma. Extracellular vesicles (EVs) are nano-sized particles used for cell communication, being increasingly regarded as potential sources of cancer biomarkers. Thus, the aim of this study was to characterize EVs from a wide range of TGCT samples, including cell lines, tissue explants and matched plasma samples from patients and healthy donors, and then use these samples to assess microRNA expression (miR-371\u2013373 cluster and let-7e). TGCT-derived EVs were successfully isolated and characterized according to MISEV guidelines. TGCT cell lines showed different levels of EV-derived miR-371\u2013373 cluster and let-7e. Upon differentiation of NT2 cells with ATRA, both cellular and EV-derived miR-371\u2013373 cluster were downregulated, whereas let-7e was upregulated. TGCT patient samples presented high levels of EV-derived miR-371\u2013373, except for the teratoma samples. We conclude that a significant portion of the circulating miR-371\u2013373 cluster used as a TGCT biomarker in the clinic is secreted into EVs, and that this cluster and the let-7 family of microRNAs may be related with TGCT intercellular communication and differentiation.<\/jats:p>","DOI":"10.1186\/s12964-025-02250-8","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:48:55Z","timestamp":1748594935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["MicroRNA-371\u2013373 cluster extracellular vesicle-based communication in testicular germ cell tumors"],"prefix":"10.1186","volume":"23","author":[{"given":"Nuno Tiago","family":"Tavares","sequence":"first","affiliation":[]},{"given":"Catarina","family":"Louren\u00e7o","sequence":"additional","affiliation":[]},{"given":"Vera","family":"Const\u00e2ncio","sequence":"additional","affiliation":[]},{"given":"Fernanda","family":"Fernandes-Pontes","sequence":"additional","affiliation":[]},{"given":"Diana","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Silva-Santos","sequence":"additional","affiliation":[]},{"given":"Isaac","family":"Braga","sequence":"additional","affiliation":[]},{"given":"Joaquina","family":"Maur\u00edcio","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Michelle","family":"Liu","sequence":"additional","affiliation":[]},{"given":"Robert S.","family":"Weiss","sequence":"additional","affiliation":[]},{"given":"Aditya","family":"Bagrodia","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"issue":"3","key":"2250_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, et al. 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