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基于细胞外囊泡的MicroRNA-371-373簇在睾丸生殖细胞肿瘤中的通讯

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

作者信息

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

机构信息

Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP) / CI-IPOP@RISE Health Research Network - Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), Porto, 4200-072, Portugal.

Doctoral Programme in Biomedical Sciences, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, 4050-313, Portugal.

出版信息

Cell Commun Signal. 2025 May 30;23(1):252. doi: 10.1186/s12964-025-02250-8.

DOI:10.1186/s12964-025-02250-8
PMID:40448114
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12124061/
Abstract

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.

摘要

睾丸生殖细胞肿瘤（TGCTs）是年轻成年人中最常见的癌症类型。微小RNA 371 - 373簇在TGCTs中高度上调，目前正在开发特异性检测miR - 371a - 3p的方法，以便作为TGCT（除畸胎瘤外）敏感且特异的生物标志物用于临床。细胞外囊泡（EVs）是用于细胞通讯的纳米级颗粒，越来越被视为癌症生物标志物的潜在来源。因此，本研究的目的是对来自广泛TGCT样本（包括细胞系、组织外植体以及患者和健康供体的匹配血浆样本）的EVs进行表征，然后使用这些样本评估微小RNA表达（miR - 371 - 373簇和let - 7e）。根据MISEV指南成功分离并表征了TGCT衍生的EVs。TGCT细胞系显示出不同水平的EV衍生的miR - 371 - 373簇和let - 7e。用全反式维甲酸（ATRA）诱导NT2细胞分化后，细胞和EV衍生的miR - 371 - 373簇均下调，而let - 7e上调。除畸胎瘤样本外，TGCT患者样本呈现高水平的EV衍生的miR - 371 - 3

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d68/12124061/df977230c194/12964_2025_2250_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d68/12124061/bbedbe75e48a/12964_2025_2250_Fig7_HTML.jpg
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本文引用的文献

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Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection.对小鼠生殖细胞肿瘤模型的分析确定了多能性相关的微小RNA作为用于生殖细胞癌检测的保守血清生物标志物。
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Urinary extracellular vesicle-derived miR-126-3p predicts lymph node invasion in patients with high-risk prostate cancer.
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据：全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.靶向恶性生殖细胞肿瘤中 miR-371~373 和 miR-302/367 簇的致癌 microRNAs 通过细胞周期破坏导致生长抑制。
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Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment.睾丸生殖细胞肿瘤细胞释放含有 microRNA 的细胞外囊泡，这些囊泡可诱导肿瘤微环境中细胞的表型和基因型改变。
Int J Cancer. 2024 Jan 15;154(2):372-388. doi: 10.1002/ijc.34697. Epub 2023 Aug 26.