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...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.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.展开更多
文摘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.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.
