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

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.

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

“…Since the impact of oxidative stress on FA has been already well discussed [28,[40][41][42], the findings reported here might be helpful for the experimental management of FA. MiR-30b-5p in this pathway may act as a tumor suppressor, repressing cell proliferation and the cell cycle [43][44][45]. It is also associated with breast cancer and NSCLC [45,46].…”

“…MiR-30b-5p in this pathway may act as a tumor suppressor, repressing cell proliferation and the cell cycle [43][44][45]. It is also associated with breast cancer and NSCLC [45,46]. MiR-1246 can influence the stemness and resistance of cancer cells to therapeutics and appears to have a role in NSCLC [21,47].…”

Genetically engineered cell-derived nanovesicles for cancer immunotherapy

“…Several studies have demonstrated that miRNAs encapsulated in native EVs derived from MSCs, such as miR-7-5p, miR-146b, miR-142-3p, and miR-let-7c, are capable of suppressing the development and metastasis of cancer. 16–18 For example, a recent study 19 by Wang et al elucidated that miR-30b-5p shuttled by bone marrow MSC-derived exosomes could promote cell apoptosis and prevent tumorigenesis in non-small cell lung cancer (NSCLC) via the EZH2/PI3K/AKT axis. Conversely, a number of studies indicated the tumor-promoting effect of MSC-derived EVs, 20–23 likely due to the enriched presence of tumor-supportive miRNAs ( e.g.…”

Advances in the role of microRNAs associated with the PI3K/AKT signaling pathway in lung cancer

“…Exocrine miR-30b-5p from bone marrow mesenchymal stem cells plays a tumor inhibitory role in NSCLC by inhibiting EZH2 and PI3K/AKT pathways. The results suggest that exocrine from bone marrow mesenchymal stem cells may be used as a new therapeutic strategy for NSCLC ( 81 ). Similarly, miR-514b-5p promotes the progress of NSCLC by targeting SGTB through PI 3-K/AKT and p38 signal pathways.…”