Open Access

ARTICLE

CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

by TAO SUN^1,2, QINGHUA SONG³, HUA LIU^1,*

1 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China
2 Department of Emergency, The People’s Hospital of Rugao, Nantong, 226500, China
3 Department of Haematology, The People’s Hospital of Rugao, Nantong, 226500, China

* Corresponding Author: HUA LIU. Email:

Oncology Research 2025, 33(1), 133-148. https://doi.org/10.32604/or.2024.054141

Received 20 May 2024; Accepted 26 August 2024; Issue published 20 December 2024

Abstract

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.

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