TUMOR-ASSOCIATED MACROPHAGES REGULATE FGD5-AS1 EXPRESSION TO PROMOTE LUNG CANCER CELL PROLIFERATION, MIGRATION, AND INVASION AND THE UNDERLYING MECHANISMS

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.