Back to Journals » International Journal of Nanomedicine » Volume 16

CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging

Authors Zhang T, Zhang P, Li HX

Received 13 July 2020

Accepted for publication 29 September 2020

Published 25 January 2021 Volume 2021:16 Pages 561—577

DOI https://doi.org/10.2147/IJN.S271976

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Tao Zhang,1 Ping Zhang,2 Hong-Xia Li3

1Department of Tuberculosis, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 2Reproductive Medicine, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 3Endoscopic Room, Linyi Chest Hospital, Linyi, Shandong 276034, People’s Republic of China

Correspondence: Hong-Xia Li
Endoscopic Room, Linyi Chest Hospital, No. 233 Fenghuang Avenue, Hedong District, Linyi, Shandong 276034, People’s Republic of China
Tel +86-13265485365
Email lihongxia4678264@163.com

Purpose: Chemoresistance is a significant barrier to the treatment and management of non-small cell lung cancer (NSCLC). Exosomes play an essential role in intercellular communication. Understanding the mechanism underlying the role of tumor stroma, especially cancer-associated fibroblasts (CAFs), during chemoresistance would significantly contribute to the clinical application of chemotherapy agents.
Results: In this study, we demonstrated that NSCLC-derived CAFs were innately resistant to cisplatin treatment and CAFs-conditioned medium significantly promoted the survival rate of NSCLC cells after cisplatin treatment. Additionally, CAFs-derived exosomes were taken up by NSCLC cells. Moreover, exosomal miRNA-130a was transferred from CAFs to recipient NSCLC cells and knockdown of miRNA-130a reversed the effect of CAFs-derived exosomes during chemoresistance of NSCLC cells. Furthermore, pumilio homolog 2 (PUM2), a RNA-binding protein, mediated the packaging of miRNA-130a into exosomes. The overexpression and knockdown of PUM2 promoted and inhibited tumor growth of xenograft mice, respectively.
Conclusion: Taken together, these results suggest that CAFs-derived exosomes confer cisplatin resistance of NSCLC cells through transferring miRNA-130a and that PUM2 is a critical factor for packaging miRNA-130a into exosomes. This study indicates that CAFs-derived exosomal miRNA-130a may be a potential therapeutic target for cisplatin resistance in NSCLC.

Keywords: chemoresistance, non-small cell lung cancer, cancer-associated fibroblasts, exosome, miRNA-130a, pumilio homolog 2

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]