Background
Lung cancer is a life-threatening disease that occurs worldwide, but is especially common in China. The crucial role of the tumour microenvironment (TME) in non-small cell lung cancer (NSCLC) has attracted recent attention. Cancer-associated fibroblasts (CAFs) are the main factors that contribute to the TME function, and CAF exosomes are closely linked to NSCLC.
Conclusions
These results provide an interesting direction for the diagnosis and therapy of NSCLC.
Methods
The expression levels of miR-3124-5p and Toll-interacting protein (TOLLIP) were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection. Fibroblasts were isolated and identified from clinical NSCLC tissues. Transmission electron microscopy and Western Blot were used to identify exosomes from these cells. Changes in proliferation (CCK-8 and clone formation), migration (wound healing), and invasion (transwell) of NSCLC cells were measured. The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP. The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.
Results
MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC. MiR-3124-5p was dramatically enriched in CAF-derived exosomes. Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes, stimulating cancer cell progression. MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression, which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC. Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway. Conclusions: These results provide an interesting direction for the diagnosis and therapy of NSCLC.