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Inhibitory role of bone marrow mesenchymal stem cells-derived exosome in non-small-cell lung cancer: microRNA-30b-5p,EZH2 and PI3K/AKT pathway |
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| Authors: | Tong Wu Qi Tian Ruiji Liu Ke Xu Shanshan Shi Xiudi Zhang Liming Gao Xiaobo Yin Shufeng Xu Ping Wang |
| Affiliation: | 1. Graduate School of Zunyi Medical University, Zunyi, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal), Writing - review & editing (equal);3. Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China Contribution: Data curation (equal), Formal analysis (equal), Resources (equal), Software (equal);4. Graduate School of Hebei Medical University, Shijiazhuang, China Contribution: Data curation (equal), Formal analysis (equal), Software (equal);5. Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China Contribution: Investigation (equal), Supervision (equal), Validation (equal);6. Graduate School of Hebei Medical University, Shijiazhuang, China Contribution: Data curation (equal), Validation (equal), Visualization (equal), Writing - review & editing (equal);7. Oncology Department, The First Hospital of Qinhuangdao, Qinhuangdao, China Contribution: Investigation (equal), Validation (equal), Visualization (equal), Writing - review & editing (equal);8. Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China Contribution: Supervision (equal), Validation (equal), Visualization (equal), Writing - review & editing (equal);9. Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China;10. Department of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing, China |
| 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. |
| Keywords: | bone marrow mesenchymal stem cells exosome EZH2 microRNA-30b-5p non-small-cell lung cancer PI3K/AKT |