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Intermittent hypoxia BMSCs-derived exosomal miR-31-5p promotes lung adenocarcinoma development via WDR5-induced epithelial mesenchymal transition 

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Abstract

Background

Intermittent hypoxia (IH) is a factor involved in the incidence and progression of lung adenocarcinoma (LUAD). Bone marrow-derived bone mesenchymal stem cells (BMSCs)-derived exosomes are related to the promotion of tumor development. The objective of this experiment was to clarify the mechanism of exosomes from BMSCs in promoting the progression of LUAD induced by IH.

Methods

This study examined if IH BMSCS-derived exosomes affect the malignancy of LUAD cells in vitro. Dual-luciferase assays were conducted to confirm the target of miR-31-5p with WD repeat domain 5 (WDR5). We further investigated whether or not  exosomal miR-31-5p or WDR5 could regulate epithelial–mesenchymal transition (EMT). We determined the effect of IH exosomes using a tumorigenesis model in vivo.

Results

miR-31-5p entered into LUAD cells via exosomes. MiR-31-5p was greatly upregulated in IH BMSCs-derived exosomes compared with RA exosomes. Increased expression of exosomal miR-31-5p induced by IH was discovered to target WDR5 directly, increased activation of WDR5, and significantly facilitated EMT, thereby promoting LUAD progression.

Conclusions

The promoting effect of IH on LUAD is achieved partly through BMSCs-derived exosomal miR-31-5p triggering WDR5 and promoting EMT.

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Data availability

The data for this study are available from the corresponding author.

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Funding

This study was funded by the National Natural Science Foundation of China (grant 82100106).

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  1. Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou City, Henan Province, China

    Jie Ren

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Ren, J. Intermittent hypoxia BMSCs-derived exosomal miR-31-5p promotes lung adenocarcinoma development via WDR5-induced epithelial mesenchymal transition . Sleep Breath 27, 1399–1409 (2023). https://doi.org/10.1007/s11325-022-02737-5

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