RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming.
RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming.
复制标题
RNA m6A 甲基化通过巨噬细胞重编程协调癌症生长和转移
DOI：
10.1038/s41467-021-21514-8
复制
发表时间：
2021-03-02
影响因子：
16.6
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Yin H;Zhang X;Yang P;Zhang X;Peng Y;Li D;Yu Y;Wu Y;Wang Y;Zhang J;Ding X;Wang X;Yang A;Zhang R
N6-甲基腺苷(M6A)是一种可逆的mRNA修饰，已被证明在多种生物过程中发挥着重要作用。然而，M6A修饰在巨噬细胞中的作用仍不清楚。在这里，我们发现消融髓系细胞中的METTL3促进了体内肿瘤的生长和转移。与野生型小鼠相比，METTL3缺陷小鼠表现出增加的M1/M2样肿瘤相关巨噬细胞和调节性T细胞对肿瘤的渗透。M6A测序显示，METTL3的缺失损害了YTHDF1介导的SPRED2的翻译，SPRED2通过ERK途径增强了NF-kB和STAT3的激活，导致肿瘤生长和转移增加。此外，PD-1检查点阻断对METTL3缺陷小鼠的治疗效果减弱，表明METTL3是肿瘤免疫治疗的潜在治疗靶点。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Lence, Tina;Akhtar, Junaid;Roignant, Jean-Yves
通讯作者：
Roignant, Jean-Yves
影响因子：
11.2
作者：
Faget, Julien;Biota, Cathy;Menetrier-Caux, Christine
通讯作者：
Menetrier-Caux, Christine
影响因子：
50.3
作者：
Li Z;Weng H;Su R;Weng X;Zuo Z;Li C;Huang H;Nachtergaele S;Dong L;Hu C;Qin X;Tang L;Wang Y;Hong GM;Huang H;Wang X;Chen P;Gurbuxani S;Arnovitz S;Li Y;Li S;Strong J;Neilly MB;Larson RA;Jiang X;Zhang P;Jin J;He C;Chen J
通讯作者：
Chen J
影响因子：
23.9
作者：
Batista, Pedro J.;Molinie, Benoit;Wang, Jinkai;Qu, Kun;Zhang, Jiajing;Li, Lingjie;Bouley, Donna M.;Lujan, Ernesto;Haddad, Bahareh;Daneshvar, Kaveh;Carter, Ava C.;Flynn, Ryan A.;Zhou, Chan;Lim, Kok-Seong;Dedon, Peter;Wernig, Marius;Mullen, Alan C.;Xing, Yi;Giallourakis, Cosmas C.;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
56.9
作者：
Liu, Jun;Do, Xiaoyang;Hei, Chuan
通讯作者：
Hei, Chuan