胞外微小RNA（miRNA）在非小细胞肺癌（NSCLC）中发挥潜在作用。本研究阐明了骨髓间充质干细胞（BMSCs）来源的外泌体载带的miR-30b-5p在治疗NSCLC中的作用。通过利用与NSCLC相关的miRNA微阵列GSE169587和mRNA数据GSE74706进行生物信息学分析，获得了差异表达的miRNA和mRNA的相关信息。预测并验证了miR-30b-5p与EZH2的关系。从BMSCs中分离和鉴定了外泌体。使用过表达miR-30b-5p的BMSCs来源的外泌体建立皮下肿瘤模型，研究miR-30b-5p、EZH2和PI3K/AKT信号通路对肿瘤生长的影响。NSCLC中共有86个BMSC-exo-miRNAs差异表达。生物信息学分析发现BMSC-exo-miR-30b-5p可通过靶向EZH2调控NSCLC进展，在体外细胞实验中得到验证。此外，miR-30b-5p的靶基因富集在PI3K/AKT信号通路中。动物实验证实BMSC-exo-miR-30b-5p通过EZH2/PI3K/AKT轴促进NSCLC细胞凋亡，抑制裸鼠中的肿瘤发生。总体而言，BMSC来源的外泌体载入的miR-30b-5p通过阻断EZH2/PI3K/AKT轴在NSCLC中发挥抑制作用。 © 2023 The Authors. 由Foundation for Cellular and Molecular Medicine和John Wiley & Sons Ltd发表的《细胞与分子医学杂志》。

Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.