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<p>Testicular germ cell tumors (TGCTs) represent the most common type of cancer in young adults. The cluster of microRNAs 371–373 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-371–373 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-371–373 cluster and let-7e. Upon differentiation of NT2 cells with ATRA, both cellular and EV-derived miR-371–373 cluster were downregulated, whereas let-7e was upregulated. TGCT patient samples presented high levels of EV-derived miR-371–373, except for the teratoma samples. We conclude that a significant portion of the circulating miR-371–373 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.</p>

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MicroRNA-371–373 cluster extracellular vesicle-based communication in testicular germ cell tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月30日

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  • Nuno Tiago Tavares,
  • Catarina Lourenço,
  • Vera Constâncio,
  • Fernanda Fernandes-Pontes,
  • Diana Fonseca,
  • Rui Silva-Santos,
  • Isaac Braga,
  • Joaquina Maurício,
  • Rui Henrique,
  • Michelle Liu,
  • Robert S. Weiss,
  • Aditya Bagrodia,
  • Carmen Jerónimo,
  • João Lobo

摘要

Testicular germ cell tumors (TGCTs) represent the most common type of cancer in young adults. The cluster of microRNAs 371–373 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-371–373 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-371–373 cluster and let-7e. Upon differentiation of NT2 cells with ATRA, both cellular and EV-derived miR-371–373 cluster were downregulated, whereas let-7e was upregulated. TGCT patient samples presented high levels of EV-derived miR-371–373, except for the teratoma samples. We conclude that a significant portion of the circulating miR-371–373 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.