BACKGROUND Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors. METHODS Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings. RESULTS miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development. CONCLUSION Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma.

中文翻译：

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间充质干细胞来源的外泌体microRNA-133b通过靶向EZH2抑制Wnt /β-catenin信号传导途径的神经胶质瘤进展。

背景技术间充质干细胞（MSC）在癌症的发生和转移中起着重要的作用，有时是通过释放外泌体来释放，这些外泌体通过传递microRNA（miRNA）来介导细胞的通讯。这项研究旨在调查MSCs的外泌体miR-133b对神经胶质瘤细胞行为的影响。方法基于微阵列的分析鉴定了神经胶质瘤中的差异表达基因（DEG）。在神经胶质瘤中阐明了EZH2和miR-133b的表达模式以及它们之间的相互作用。改变神经胶质瘤细胞中miR-133b和EZH2的表达，以检查其对细胞活性的作用。此外，将神经胶质瘤细胞与用miR-133b模拟物或抑制剂处理的MSC来源的外泌体，和过表达EZH2的载体或针对EZH2的shRNA共培养，以表征其对增殖，侵袭，胶质瘤细胞的体外迁移 还进行了体内测定以验证体外发现。结果在胶质瘤组织和细胞中，miR-133b被下调，而EZH2被上调。发现miR-133b靶向并负调控EZH2表达。此外，EZH2沉默导致神经胶质瘤细胞增殖，侵袭和迁移受到抑制。此外，包含miR-133b的MSC衍生的外泌体通过抑制EZH2和Wnt /β-catenin信号通路抑制了神经胶质瘤细胞的增殖，侵袭和迁移。此外，体内实验证实了MSC衍生的外泌体miR-133b对神经胶质瘤发展的肿瘤抑制作用。结论集体而言，