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

Background/Aims: 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...

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Bibliographic Details
Main Authors: Jie Zhu, Dengliang Liu, Yingying Zou
Format: Article
Language:English
Published: AVES 2025-06-01
Series:The Turkish Journal of Gastroenterology
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Online Access:https://www.turkjgastroenterol.org/en/m6a-methylation-regulator-rbm15-mediated-upregulation-of-itgbl1-mrna-stability-aggravates-colon-adenocarcinoma-progression-by-remodeling-the-tumor-microenvironment-137379
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Summary:Background/Aims: 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. Materials and Methods: TIMER and UALCAN databases were applied to analyze the relationship between COAD and Integrin !-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. Results: 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. Conclusion: RBM15 could promote COAD progression by regulating ITGBL1 mRNA stability, providing a promising biomarker and a potential target for COAD.
ISSN:2148-5607