Exosomal microRNAs (miRNAs) have been implicated in the development and progression of a variety of tumors; however, whether they contribute to medulloblastoma (MB) tumorigenesis remains to be elucidated. To address this, we first characterized the miRNA profiles of circulating exosomes by miRNA sequencing to identify miRNAs differentially expressed between children with MB and healthy controls. Then, we conducted in vitro and in vivo functional assays with the identified miRNAs and their predicted targets. We found that, compared with healthy controls, 35 miRNAs were upregulated and 5 downregulated in exosomes isolated from the plasma of MB patients. We further found that the expression of miR-101-3p and miR-423-5p was significantly higher in plasma exosomes from MB patients than in healthy controls in an expanded cohort and these exosomal miRNAs could be delivered to tumor cells via exosomes. An in vitro functional analysis of miR-101-3p and miR-423-5p showed that treating MB cells with the corresponding mimics significantly inhibited the proliferation, colony-forming ability, migratory ability, and invasive capacity of tumor cells, and promoted cell apoptosis. Additionally, miR-101-3p and miR-423-5p were found to act as tumor suppressors by directly targeting a common gene, FOXP4, which encodes a transcription factor with a vital role in embryonic development and tumorigenesis. Moreover, miR-101-3p also targeted EZH2, a histone methyltransferase, to reinforce its tumor inhibitory effects. Using a xenograft nude mouse model of MB, we further identified that the overexpression of miR-101-3p and miR-423-5p inhibited tumorigenesis in vivo. Our findings provide novel insights into the functions of exosomal miRNAs in mediating MB progression and suggest a potential therapeutic approach for the treatment of children with MB.

外泌体 microRNA (miRNA) 与多种肿瘤的发生和发展有关；然而，它们是否有助于成神经管细胞瘤 (MB) 的肿瘤发生仍有待阐明。为了解决这个问题，我们首先通过 miRNA 测序来表征循环外泌体的 miRNA 图谱，以鉴定 MB 儿童和健康对照儿童之间差异表达的 miRNA。然后，我们对已鉴定的 miRNA 及其预测靶标进行了体外和体内功能测定。我们发现，与健康对照相比，从 MB 患者血浆中分离出的外泌体中有 35 种 miRNA 上调，5 种下调。我们进一步发现，在扩展队列中，MB 患者血浆外泌体中 miR-101-3p 和 miR-423-5p 的表达显着高于健康对照，并且这些外泌体 miRNA 可以通过外泌体递送至肿瘤细胞。miR-101-3p 和 miR-423-5p 的体外功能分析表明，用相应的模拟物处理 MB 细胞可显着抑制肿瘤细胞的增殖、集落形成能力、迁移能力和侵袭能力，并促进细胞凋亡. 此外，miR-101-3p 和 miR-423-5p 被发现通过直接靶向共同基因来充当肿瘤抑制因子，集落形成能力、迁移能力和侵袭能力，促进细胞凋亡。此外，miR-101-3p 和 miR-423-5p 被发现通过直接靶向共同基因来充当肿瘤抑制因子，集落形成能力、迁移能力和侵袭能力，促进细胞凋亡。此外，miR-101-3p 和 miR-423-5p 被发现通过直接靶向共同基因来充当肿瘤抑制因子，FOXP4，它编码的转录因子在胚胎发育和肿瘤发生中起着至关重要的作用。此外，miR-101-3p 还靶向组蛋白甲基转移酶EZH2，以增强其肿瘤抑制作用。使用 MB 的异种移植裸鼠模型，我们进一步确定了 miR-101-3p 和 miR-423-5p 的过表达抑制了体内的肿瘤发生。我们的研究结果为外泌体 miRNA 在介导 MB 进展中的功能提供了新的见解，并提出了治疗 MB 儿童的潜在治疗方法。