2026-10-12T09:40:06Z https://www.scidb.cn/oai

10.57760/sciencedb.j00217.00bds 2026-09-29T15:43:30Z

2026-09-29 TUMOR-ASSOCIATED MACROPHAGES REGULATE FGD5-AS1 EXPRESSION TO PROMOTE LUNG CANCER CELL PROLIFERATION, MIGRATION, AND INVASION AND THE UNDERLYING MECHANISMS doi:10.57760/sciencedb.j00217.00bds en Objective To investigate the effect of tumor-associated macrophages (TAMs) on FGD5-AS1 expression in lung cancer cells and to explore the potential molecular mechanisms underlying their effects on lung cancer cell proliferation, migration, and invasion.Methods THP-1 cells were induced to differentiate into M0 and M2 macrophages using phorbol 12-myristate 13-acetate (PMA), followed by treatment with interleukin-4 (IL-4) and interleukin-13 (IL-13). Macrophage differentiation was assessed by morphological observation, quantitative real-time PCR (qPCR), and immunofluorescence staining. Conditioned media (CM) from M0 and M2 macrophages, as well as M2 macrophages treated with the exosome-release inhibitor GW4869, were collected and used to treat A549 and H1299 lung cancer cells. FGD5-AS1 was silenced using small interfering RNA (siRNA). Cell proliferation, migration, and invasion were evaluated using 5-ethynyl-2′-deoxyuridine (EdU) incorporation and Transwell assays, while apoptosis-related proteins were examined by Western blotting. RNA sequencing (RNA-seq) was subsequently performed in A549 cells subjected to different treatments to identify genes and signaling pathways potentially involved in FGD5-AS1-mediated regulation.Results Compared with M0 macrophages, M2 macrophages exhibited characteristic morphological changes and significantly higher expression levels of Arg-1, CCL18, IL-10, and CD206, accompanied by increased FGD5-AS1 expression (P < 0.001). Treatment with M2-CM markedly enhanced the proliferation, migration, and invasion of A549 and H1299 cells and reduced apoptosis. These effects were substantially attenuated following FGD5-AS1 knockdown. Inhibition of exosome release with GW4869, either alone or in combination with FGD5-AS1 knockdown, did not significantly alter the proliferative effect induced by M2-CM. RNA-seq analysis showed that FGD5-AS1-associated differentially expressed genes were mainly enriched in DNA replication, DNA repair, cell division, cell cycle, and the Fanconi anemia pathway, as well as the IL-17 and TNF signaling pathways.Conclusion M2 macrophages promote the proliferation, migration, and invasion of lung cancer cells, at least in part through regulation of FGD5-AS1. These findings provide new insights into the interaction between TAMs and lung cancer cells and suggest that the M2 macrophage-FGD5-AS1 axis may represent a potential target for intervention in the tumor microenvironment. lung cancer; M2 macrophages; FGD5-AS1; exosomes; RNA sequencing 陈益平 王汉桂 宋政 杨利杰 王靖 PUBLIC https://creativecommons.org/publicdomain/zero/1.0/ dataset Science Data Bank