Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small cell lung cancer
Lin Shi
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorWeiliang Zhu
Department of Cancer Center, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorYuanyuan Huang
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Search for more papers by this authorLin Zhuo
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorSiyun Wang
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorShaobing Chen
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Bei Zhang
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Correspondence
Bei Zhang and Bin Ke, Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Guangdong, China.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Bin Ke
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Correspondence
Bei Zhang and Bin Ke, Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Guangdong, China.
Email: [email protected]; [email protected]
Search for more papers by this authorLin Shi
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorWeiliang Zhu
Department of Cancer Center, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorYuanyuan Huang
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Search for more papers by this authorLin Zhuo
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorSiyun Wang
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorShaobing Chen
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Bei Zhang
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Correspondence
Bei Zhang and Bin Ke, Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Guangdong, China.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Bin Ke
Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Correspondence
Bei Zhang and Bin Ke, Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Guangdong, China.
Email: [email protected]; [email protected]
Search for more papers by this authorLin Shi and Weiliang Zhu contributed equally to this work and shared co-first authorship.
Abstract
Background
Cancer-associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored the ability of microRNA-20a (miR-20a) within these CAF-derived exosomes to influence non-small-cell lung cancer (NSCLC) progression.
Materials and methods
Normal tissue-associated fibroblasts (NAFs) and CAFs were collected from samples of NSCLC patient tumors and paracancerous lung tissues. Exosomes derived from these cells were then characterized via Western blotting, nanoparticle tracking analyses, and transmission electron microscopy. The expression of miR-20a was assessed via qPCR and fluorescence in situ hybridization (FISH). CCK-8, EdU uptake, and colony formation assessments were used for evaluating tumor proliferation, while Hoechst staining was performed to monitor the in vitro apoptotic death of tumor cells. A model of xenograft tumor established in nude mice was also used to evaluate in vivo tumor responses.
Results
CAF-derived exosomes exhibited miR-20a upregulation and promoted NSCLC cell proliferation and resistance to cisplatin (DDP). Mechanistically, CAF-derived exosomes were discovered to transmit miR-20a to tumor cells wherein it was able to target PTEN to enhance DDP resistance and proliferation. Associated PTEN downregulation following exosome-derived miR-20a treatment enhanced PI3K/AKT pathway activation.
Conclusion
The achieved outcomes explain that CAFs can release miR-20a-containing exosomes capable of promoting NSCLC progression and chemoresistance, highlighting this pathway as a possible therapeutic target in NSCLC.
CONFLICT OF INTEREST
The authors have no relevant financial or non-financial interests to disclose.
Supporting Information
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| ctm2989-sup-0001-SuppMat.docx1.2 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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