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骨髓间充质干细胞来源的外泌体在非小细胞肺癌中的抑制作用：miRNA-30b-5p、EZH2 和 PI3K/AKT 通路。

Inhibitory role of bone marrow mesenchymal stem cells-derived exosome in non-small-cell lung cancer: microRNA-30b-5p, EZH2 and PI3K/AKT pathway.

机构信息

Graduate School of Zunyi Medical University, Zunyi, China.

Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China.

出版信息

J Cell Mol Med. 2023 Nov;27(22):3526-3538. doi: 10.1111/jcmm.17933. Epub 2023 Sep 12.

DOI:10.1111/jcmm.17933
PMID:37698037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10660609/
Abstract

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.

摘要

外泌体 microRNA（miRNA）在非小细胞肺癌（NSCLC）中发挥重要作用。本研究阐明了骨髓间充质干细胞（BMSCs）来源的外泌体转运的 miR-30b-5p 在治疗 NSCLC 中的作用。通过 NSCLC 相关 miRNA 微阵列 GSE169587 和 mRNA 数据 GSE74706 进行生物信息学分析，以收集差异表达的 miRNAs 和 mRNAs。预测并验证了 miR-30b-5p 与 EZH2 的关系。分离 BMSCs 来源的外泌体并进行鉴定。用 BMSCs 来源的过表达 miR-30b-5p 的外泌体建立皮下肿瘤发生模型，以研究 miR-30b-5p、EZH2 和 PI3K/AKT 信号通路对肿瘤生长的影响。NSCLC 中 86 种 BMSC-exo-miRNAs 表达差异。生物信息学分析发现，BMSC-exo-miR-30b-5p 通过靶向 EZH2 调节 NSCLC 进展，这通过体外细胞实验得到验证。此外，miR-30b-5p 的靶基因富集在 PI3K/AKT 信号通路中。动物实验验证了 BMSC-exo-miR-30b-5p 通过 EZH2/PI3K/AKT 轴促进 NSCLC 细胞凋亡并预防裸鼠肿瘤发生。综上所述，BMSC 来源的外泌体负载的 miR-30b-5p 通过阻断 EZH2/PI3K/AKT 轴抑制 NSCLC 的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/bb927b499e15/JCMM-27-3526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/90b4bd76a451/JCMM-27-3526-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/bb927b499e15/JCMM-27-3526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/90b4bd76a451/JCMM-27-3526-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/1777836dcdb0/JCMM-27-3526-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/22f91608e542/JCMM-27-3526-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd69/10660609/325d607e77ea/JCMM-27-3526-g005.jpg
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