PTEN公司
癌症研究
PI3K/AKT/mTOR通路
蛋白激酶B
小RNA
肿瘤科
肺癌
癌症
癌相关成纤维细胞
医学
生物
信号转导
癌细胞
细胞生物学
内科学
基因
生物化学
作者
Lin Shi,Wei Zhu,Yuanyuan Huang,Lin Zhuo,Siyun Wang,Shaobing Chen,Bei Zhang,Bin Ke
摘要
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.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.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.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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