ORIGINAL PAPER
METTL1-mediated m7G modification of CD47 promotes lung adenocarcinoma escape from macrophage phagocytosis
1
Department of Pathology, People’s Hospital of Anji, Huzhou 313300, Zhejiang, China
Submission date: 2025-07-15
Final revision date: 2026-01-14
Acceptance date: 2026-01-21
Online publication date: 2026-09-30
Corresponding author
KEYWORDS
ABSTRACT
Introduction:
Emerging evidence suggests that reduced phagocytosis by macrophages is a significant event contributing to the immune escape of cancer cells. METTL1 has been implicated in the malignant progression of various cancers, but whether it affects macrophage phagocytosis of lung adenocarcinoma (LUAD) remains unclear.
Material and Methods:
METTL1 expression was analyzed using The Cancer Genome Atlas (TCGA) database and LUAD cell models. The impact of METTL1 expression on macrophage phagocytosis of LUAD was analyzed using CFSE staining and flow cytometry based on METTL1 knockdown and overexpression cell models. Prediction via the RM2Target database identified the gene CD47, which might be regulated by METTL1 through m7G modification. Meanwhile, RIP-qPCR, qPCR, and MeRIP-qPCR were used to detect the effects of METTL1-regulated m7G modification on CD47 mRNA levels, and rescue experiments were designed to explore its regulatory effect on macrophage phagocytic ability.
Results:
METTL1 was highly expressed in LUAD tissues and cells. Higher METTL1 expression was associated with poor patient prognosis. Knockdown of METTL1 enhanced macrophage phagocytosis by approximately 109%, whereas its overexpression reduced phagocytosis by about 54%. Mechanistic research showed that METTL1, through its methyltransferase activity, mediates m7G modification of CD47 mRNA, thereby enhancing its stability and increasing its expression, promoting LUAD escape from macrophage phagocytosis.
Conclusions:
Taken together, our study demonstrates that METTL1-driven m7G modification of CD47 promotes LUAD escape from macrophage phagocytosis, suggesting that targeting the METTL1-CD47 axis may represent a potential strategy for enhancing LUAD immunotherapy.
Emerging evidence suggests that reduced phagocytosis by macrophages is a significant event contributing to the immune escape of cancer cells. METTL1 has been implicated in the malignant progression of various cancers, but whether it affects macrophage phagocytosis of lung adenocarcinoma (LUAD) remains unclear.
Material and Methods:
METTL1 expression was analyzed using The Cancer Genome Atlas (TCGA) database and LUAD cell models. The impact of METTL1 expression on macrophage phagocytosis of LUAD was analyzed using CFSE staining and flow cytometry based on METTL1 knockdown and overexpression cell models. Prediction via the RM2Target database identified the gene CD47, which might be regulated by METTL1 through m7G modification. Meanwhile, RIP-qPCR, qPCR, and MeRIP-qPCR were used to detect the effects of METTL1-regulated m7G modification on CD47 mRNA levels, and rescue experiments were designed to explore its regulatory effect on macrophage phagocytic ability.
Results:
METTL1 was highly expressed in LUAD tissues and cells. Higher METTL1 expression was associated with poor patient prognosis. Knockdown of METTL1 enhanced macrophage phagocytosis by approximately 109%, whereas its overexpression reduced phagocytosis by about 54%. Mechanistic research showed that METTL1, through its methyltransferase activity, mediates m7G modification of CD47 mRNA, thereby enhancing its stability and increasing its expression, promoting LUAD escape from macrophage phagocytosis.
Conclusions:
Taken together, our study demonstrates that METTL1-driven m7G modification of CD47 promotes LUAD escape from macrophage phagocytosis, suggesting that targeting the METTL1-CD47 axis may represent a potential strategy for enhancing LUAD immunotherapy.
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