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

被引:101
作者
Shi, Lin [1 ]
Zhu, Weiliang [2 ]
Huang, Yuanyuan [3 ]
Zhuo, Lin [1 ]
Wang, Siyun [1 ]
Chen, Shaobing [1 ]
Zhang, Bei [3 ]
Ke, Bin [3 ]
机构
[1] Southern Med Univ, Dept Tradit Chinese Med, Zhujiang Hosp, Guangzhou, Peoples R China
[2] Southern Med Univ, Dept Canc Ctr, Zhujiang Hosp, Guangzhou, Peoples R China
[3] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept VIP Reg, State Key Lab Oncol South China,Canc Ctr, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China
来源
CLINICAL AND TRANSLATIONAL MEDICINE | 2022年 / 12卷 / 07期
基金
中国国家自然科学基金;
关键词
CAF; exosome; microRNA-20a; NSCLC; PTEN; TUMOR MICROENVIRONMENT; COLORECTAL-CANCER; METASTASIS; INHIBITION; THERAPY; MIRNAS; GROWTH; LOOP; PROLIFERATION; ANGIOGENESIS;
D O I
10.1002/ctm2.989
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:24
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