Extracellular vesicle‐encapsulated microRNA‐425‐derived from drug‐resistant cells promotes non‐small–cell lung cancer progression through DAPK1‐medicated PI3K/AKT pathway.

Investigations in the area of tumor‐derived extracellular vesicles (EVs) open a new horizon in developing cancer biology and its potential as cancer biomarkers. Following this prospect, we aimed to identify that the role of successfully isolated EVs from drug‐resistance cells in the progression of non‐small–cell lung cancer (NSCLC). P‐EVs and R‐EVs secreted by A549 cells and drug‐resistant A549‐R cells respectively were extracted and characterized. The targeting relationship between miR‐425 and MED1 was verified. Cell proliferation, invasion, migration and apoptosis after treatment of P‐EVs, R‐EVs, miR‐425 inhibitor, miR‐425 mimic, pcDNA‐MED1, or phosphatidylinositol‐3‐kinase (PI3K)/AKT inhibitor LY294002 were detected. Furthermore, xenograft tumor in nude mice was established for further confirming our in vitro findings. P‐EVs and R‐EVs were successfully extracted and could be internalized by A549 cells. A549‐R cells and R‐EVs showed higher miR‐425 expression compared with A549 cells and P‐EVs, respectively. miR‐425 delivered by R‐EVs could promote the proliferation, migration, and invasion, while inhibit apoptosis of NSCLC cells. MED1 was the target gene of miR‐425. EVs‐encapsulated miR‐425‐derived from A549‐R cells could promote the progression of NSCLC in vivo through regulating DAPK1‐medicated PI3K/AKT pathway. Moreover, miR‐425 delivered by R‐EVs promoted tumorigenesis in vivo. Taken together, the result suggested that EVs‐delivered miR‐425‐derived from A549‐R cells promoted the progression of NSCLC through regulating DAPK1‐medicated PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]