[No authors listed]
Cancerâassociated fibroblasts (CAFs) exhibit tumorâstimulating properties and are associated with poor survival in several types of cancer, making them potential therapeutic targets. The present study aimed to determine whether CAFs were associated with cell migration and invasion in lung squamous cell carcinoma (LUSC), as well as their association with microRNAâ369 (miRâ369) in these processes. Firstly, the changes of the malignant biological behavior were observed by treating the LUSC cells with the CAFsâderived extracellular vesicles (CAFsâEVs). Subsequently, the differentially expressed miRNAs in the cells treated with CAFsâEVs were analyzed by microarray analysis. Following inhibition of miRâ369 expression in CAFsâEVs, LUSC cells were coâcultured, and the malignant biological behavior of the cells was reâexamined. Then, through bioinformatics analysis and verification, the mRNA targets of miRâ369 and the corresponding downstream signaling pathway were screened out. Finally, the effects of CAFsâEVs on the growth and metastasis of LUSC were demonstrated by in vivo tumor formation and metastasis experiments. It was identified that miRâ369 was expressed at a relatively high level in the CAFsâEVs. Neurofibrominâ1 (NF1) was hypothesized as a direct target of miRâ369 in LUSC. Also, the overexpression of miRâ369 activated the mitogenâactivated protein kinase signaling pathway by interacting with NF1, consequently potentiating LUSC cell growth. The present study provided novel insights into the action of miRâ369 in CAFsâEVs in controlling LUSC cell migration, invasion and tumorigenesis, and identified miRâ369 in CAFsâEVs as an important prognostic marker and therapeutic target.
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