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m6A甲基转移酶METTL3通过抑制RIG-I-MAVS天然免疫途径促进非小细胞肺癌进展。

m6A methyltransferase METTL3 promotes non-small-cell lung carcinoma progression by inhibiting the RIG-I-MAVS innate immune pathway.

作者信息

Huang Tinghui, Ao Xudong, Liu Jie, Sun Chuancheng, Dong Yunfei, Yin Xuechen, Zhang Yan, Wang Xinping, Li Wenying, Cao Jiujiu, Pan Feiyan, Hu Zhigang, Guo Zhigang, He Lingfeng

机构信息

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.

Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University. No. 42, Zhaowuda Road, Saihan District, Hohhot, Inner Mongolia Autonomous Region, 010000, China.

出版信息

Transl Oncol. 2025 Jan;51:102230. doi: 10.1016/j.tranon.2024.102230. Epub 2024 Dec 2.

DOI:10.1016/j.tranon.2024.102230
PMID:39626341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11652952/
Abstract

Our experimental study showed that METTL3 was highly expressed in NSCLC cells and promoted the growth of tumor cells. METTL3 takes N6-methyladenosine (m6A) as the main means of mRNA modification to control the expression and function of RIG-I-MAVS signalling pathway. RIG-I-MAVS constitute the first line frontier in the innate immune defense of human cells. Activation of RIG-I-MAVS signaling can inhibit tumor cell growth and activate the immune microenvironment. Our experimental data reveal that lung cancer cells utilize METTL3-mediated methylation modifications to inhibit the activation of RIG-I-MAVS signaling pathway and immune responses. Our work provides new ideas for biotherapy and immunotherapy.

摘要

我们的实验研究表明，METTL3在非小细胞肺癌（NSCLC）细胞中高表达，并促进肿瘤细胞生长。METTL3以N6-甲基腺苷（m6A）作为mRNA修饰的主要方式，来调控RIG-I-MAVS信号通路的表达和功能。RIG-I-MAVS构成人体细胞固有免疫防御的第一道前沿防线。RIG-I-MAVS信号的激活可抑制肿瘤细胞生长并激活免疫微环境。我们的实验数据表明，肺癌细胞利用METTL3介导的甲基化修饰来抑制RIG-I-MAVS信号通路的激活及免疫反应。我们的工作为生物治疗和免疫治疗提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/426bd0dd962a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/61cda8ef2aee/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/7248077cbba7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/1e9e07a306bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/18ac70a89027/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/aade6fb62b68/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/dde4a8a8ee1a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/a9f6066100fc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/426bd0dd962a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/61cda8ef2aee/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/7248077cbba7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/1e9e07a306bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/18ac70a89027/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/aade6fb62b68/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/dde4a8a8ee1a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/a9f6066100fc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb0/11652952/426bd0dd962a/gr7.jpg

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本文引用的文献

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Int J Biol Sci. 2023 Mar 5;19(5):1616-1632. doi: 10.7150/ijbs.79467. eCollection 2023.
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METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy.
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METTL3-mediated m6A mRNA methylation regulates neutrophil activation through targeting TLR4 signaling.METTL3介导的m6A mRNA甲基化通过靶向TLR4信号传导调节中性粒细胞活化。
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