Hypoxic non-small-cell lung cancer cell-derived exosomal miR-21 promotes resistance of normoxic cell to cisplatin
Received 11 September 2018
Accepted for publication 31 January 2019
Published 12 March 2019 Volume 2019:12 Pages 1947—1956
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr William Cho
Caijun Dong,1 Xingwang Liu,2 Huisheng Wang,3 Jutao Li,4 Lei Dai,5 Jun Li,6 Zhen Xu1
1Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Sports Medicine Center, Department of Sports Medicine and Arthroscopy Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Orthopedics, The People’s Hospital of China Medical University, Shenyang, People’s Republic of China; 4Department of Hand and Foot Surgery I, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Liaoning, People’s Republic of China; 5Department of Thyroid Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 6Department of General Surgery II, Taihe Hospital, Shiyan, Hubei, People’s Republic of China
Purpose: To explore the effects of hypoxic non-small-cell lung cancer (NSCLC)-derived exosomes on NSCLC resistance to cisplatin.
Materials and methods: Exosomes were isolated by differential centrifugation and characterized by transmission electron microscope and Western blotting. Quantitative real-time PCR was used to measure miR-21 levels. MTT assays and colony formation assays were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance.
Results: Hypoxic NSCLC cell-derived exosomes facilitate normoxic cell resistance to cisplatin. In addition, hypoxia enhanced the miR-21 expression in NSCLC cells and cell-derived exosomes. Interestingly, changes in miR-21 levels in the hypoxia-induced exosomes affected the sensitivity of recipient cells to cisplatin. Mechanically, exosomal miR-21 promoted cisplatin resistance by downregulating phosphatase and tensin homolog (PTEN). The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN. Moreover, high miR-21 expression was associated with shorter median survival period in patients undergoing pharmacotherapy, but no association was observed in patients who were not under pharmacotherapy.
Conclusion: Exosomal miR-21 derived from hypoxic NSCLC cells may promote cisplatin resistance, which indicates that exosomal miR-21 might be a potential biomarker and therapeutic target to address NSCLC chemoresistance.
Keywords: non-small-cell lung cancer, exosomes, miR-21, cisplatin resistance, PTEN
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]