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.

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.

Shi L ，Zhu W ，Huang Y ，Zhuo L ，Wang S ，Chen S ，Zhang B ，Ke B ... -  《Clinical and Translational Medicine》

MicroRNA-25-3p promotes cisplatin resistance in Non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT route.

Sun B ，Hu N ，Cong D ，Chen K ，Li J ... -  《-》

Cancer-associated fibroblasts secreted miR-103a-3p suppresses apoptosis and promotes cisplatin resistance in non-small cell lung cancer.

Wang H ，Huang H ，Wang L ，Liu Y ，Wang M ，Zhao S ，Lu G ，Kang X ... -  《Aging-US》

Downregulated exosomal microRNA-148b-3p in cancer associated fibroblasts enhance chemosensitivity of bladder cancer cells by downregulating the Wnt/β-catenin pathway and upregulating PTEN.

Shan G ，Zhou X ，Gu J ，Zhou D ，Cheng W ，Wu H ，Wang Y ，Tang T ，Wang X ... -  《-》

MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis.

Lu C ，Shan Z ，Hong J ，Yang L ... -  《-》