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Pirfenidone promotes the levels of exosomal miR-200 to down-regulate ZEB1 and represses the epithelial-mesenchymal transition of non-small cell lung cancer cells

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Abstract

Non-small cell lung cancer (NSCLC) is the malignancy with highest mortality and morbidity. Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells in the tumor microenvironment of NSCLC. This research is performed to explore the biological functions of pirfenidone (PFD) to repress the malignant phenotypes of NSCLC cells, and its regulatory effects on exosomal microRNA-200 (exo-miR-200) derived from CAFs. In the present work, we report that, exo-miR-200 secreted by CAFs restrains the migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells; PFD treatment promotes the secretion of exo-miR-200 from CAFs and enhances the tumor-suppressive properties of exo-miR-200 on NSCLC cells; zinc finger E-box binding homeobox 1 (ZEB1) is identified as a target of miR-200, and PFD treatment repressed the expression of ZEB1 in NSCLC cells via inducing the expression and secretion of miR-200 in CAFs. In conclusion, PFD-induced miR-200 overexpression in CAFs inhibits ZEB1 expression in NSCLC cells, and thus decelerates the migration, invasion and EMT process. Our study may provide clues for the treatment of NSCLC.

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Funding

The research was supported by Natural Science Foundation of Hunan Province Youth Fund Project (2020JJ5912).

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Authors and Affiliations

  1. Center of Respiratory Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Rd, Changsha, 410008, Hunan, China

    Jingjing Liu, Liming Cao, Yuanyuan Li, Pengbo Deng, Pinhua Pan, Chengping Hu & Huaping Yang

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  1. Jingjing Liu
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  2. Liming Cao
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  3. Yuanyuan Li
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  4. Pengbo Deng
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  5. Pinhua Pan
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  6. Chengping Hu
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  7. Huaping Yang
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Corresponding author

Correspondence to Huaping Yang.

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The study was performed in accordance with the Declaration of Helsinki and obtained the approval from the Ethics Committee of Xiangya Hospital (Approval no. 2016A0388).

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Liu, J., Cao, L., Li, Y. et al. Pirfenidone promotes the levels of exosomal miR-200 to down-regulate ZEB1 and represses the epithelial-mesenchymal transition of non-small cell lung cancer cells. Human Cell 35, 1813–1823 (2022). https://doi.org/10.1007/s13577-022-00766-6

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  • DOI: https://doi.org/10.1007/s13577-022-00766-6

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