METTL14 promotes the malignant proliferation of Ewing sarcoma cells and induces the M2 polarization of tumor-associated macrophages via the FOXP4-AS1/miR-107/FAM98A axis

Abnormalities in the tumor immune microenvironment function as a key role in Ewing sarcoma (ES). This study aims to explain the effect of METTL14 on the polarization of tumor-associated macrophage (TAM) in the ES tumor immune microenvironment. METTL14, FOXP4-AS1, miR-107, and FAM98A were detected. Cell viability and proliferation were assayed. ES cells underwent co-culture with THP-1-induced macrophages, followed by measurement of M1 and M2 macrophage polarization, TNF-α, IL-12, IL-10, TGF-β, PCNA, iNOS, and Arg-1. FOXP4-AS1 stability was analyzed. m6A enrichment on FOXP4-AS1 was assessed. The subcellular localization of FOXP4-AS1 was detected. The bindings between FOXP4-AS1 and miR-107, as well as between miR-107 and FAM98A, were verified. METTL14, FOXP4-AS1, and FAM98A exhibited high expression, while miR-107 was lowly expressed in ES. METTL14 knockdown suppressed ES cell proliferation and promoted the M1 polarization of TAM. METTL14 promoted FOXP4-AS1 expression through m6A modification. FOXP4-AS1 bound to miR-107, and miR-107 inhibited FAM98A expression. Overexpression of FOXP4-AS1 or FAM98A, or miR-107 inhibition, could partly reverse the suppressive effect of METTL14 silencing on the ES cell proliferation and the promoting effect on the M1 polarization of TAM. In conclusion, METTL14 promotes ES cell proliferation and the M2 polarization of TAM through the FOXP4-AS1/miR-107/FAM98A axis.