m6A Methylation Regulator RBM15-Mediated Upregulation of ITGBL1 mRNA Stability Aggravates Colon Adenocarcinoma Progression by Remodeling the Tumor Microenvironment.

Colon adenocarcinoma (COAD) is a prevalent malignant tumor of the digestive system. Previous research has indicated that RNA N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein-15 (RBM15) is involved in various cancers. We aimed to investigate the function of RBM15 in COAD progression and its underlying molecular mechanism. TIMER and UALCAN databases were applied to analyze the relationship between COAD and Integrin β-like 1 protein (ITGBL1) or RBM15. RT-qPCR and Western blot were used to analyze ITGBL1, M2-type macrophage markers, EMT-related markers, and RBM15 expression. CCK-8, colony formation, and transwell experiments detected cell viability, proliferation, migration, and invasion. The effect of ITGBL1 on COAD tumor growth was examined using a xenograft tumor model. The effects of COAD cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry analysis. Relationships between RBM15 and ITGBL1 were validated using MeRIP and dual-luciferase reporter assay. ITGBL1 and RBM15 contents were elevated in COAD. ITGBL1 knockdown could hinder COAD cell proliferation, migration, invasion, M2-type macrophage polarization, and lymphocyte immunity. Meanwhile, the lack of RBM15 dampened tumor growth in vivo. Mechanistically, RBM15 could increase ITGBL1 expression by m6A methylation. RBM15 could promote COAD progression by regulating ITGBL1 mRNA stability, providing a promising biomarker and a potential target for COAD.