| Literature DB >> 33654093 |
Huilong Yin1,2,3,4, Xiang Zhang3, Pengyuan Yang5, Xiaofang Zhang3, Yingran Peng3, Da Li3, Yanping Yu6, Ye Wu3, Yidi Wang7, Jinbao Zhang3, Xiaochen Ding8, Xiangpeng Wang2,4, Angang Yang9,10,11, Rui Zhang12,13.
Abstract
N6-methyladenosine (m6A) is a reversible mRNA modification that has been shown to play important roles in various biological processes. However, the roles of m6A modification in macrophages are still unknown. Here, we discover that ablation of Mettl3 in myeloid cells promotes tumour growth and metastasis in vivo. In contrast to wild-type mice, Mettl3-deficient mice show increased M1/M2-like tumour-associated macrophage and regulatory T cell infiltration into tumours. m6A sequencing reveals that loss of METTL3 impairs the YTHDF1-mediated translation of SPRED2, which enhances the activation of NF-kB and STAT3 through the ERK pathway, leading to increased tumour growth and metastasis. Furthermore, the therapeutic efficacy of PD-1 checkpoint blockade is attenuated in Mettl3-deficient mice, identifying METTL3 as a potential therapeutic target for tumour immunotherapy.Entities:
Mesh：
Substances：
Year: 2021 PMID： 33654093 PMCID： PMC7925544 DOI： 10.1038/s41467-021-21514-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919