【原】Gastroenterology（IF=33.88）| METTL3通过激活m6A-GLUT1- mTORC1轴促进结直肠癌发生

GCTA 2022-08-30 发布于广东

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RNA-N6甲基腺苷甲基转移酶METTL3通过激活m6A-GLUT1- mTORC1轴促进结直肠癌发生，同时也是该疾病的治疗靶点。

Gastroenterology(IF=33.88)|文章标题：

RNA N6 -Methyladenosine Methyltransferase METTL3 Facilitates Colorectal Cancer by Activating the m6 A-GLUT1-mTORC1 Axis and Is a Therapeutic Target

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【背景】

RNA m6A修饰是人类细胞中最丰富的RNA修饰，也是信使RNA (mRNA)剪接、翻译和降解的转录后调控的关键决定因素。该修饰的动态调控对于细胞各项生命活动的维持和细胞周期的推进有重要意义。

【本研究发现】

METTL3是结直肠癌发生中必需的m6A调节酶。
METTL3通过诱导m6A-GLUT1-mTORC1轴促进CRC的启动和进展。
MTase 结构域中的保守基序（DPPW、IHM 和RTGRTGH）对于CRC中的METTL3功能很重要。
mTORC1的抑制增强了METTL3沉默在CRC中的抗癌作用。

图文摘要：利用CRISPR-Cas9筛选技术在CRC细胞、患者细胞衍生的类器官、小鼠模型研究METTL3 的作用

-原文摘要句式分析&翻译-

BACKGROUND & AIMS: RNA N6 -methyladenosine (m6 A) modification has recently emerged as a new regulatory mechanism in cancer progression. We aimed to explore the role of the m6 A regulatory enzyme METTL3 in colorectal cancer (CRC) pathogenesis and its potential as a therapeutic target.

背景与目的：RNA N6-甲基腺苷（m6 A）修饰是一种最近才被发现的癌症进展调节机制。我们旨在探讨m6 A调节酶METTL3在结直肠癌（CRC）发病机制中的作用及其作为治疗靶点的潜力。

机制➪应用。

METHODS: The expression and clinical implication of METTL3 were investigated in multiple human CRC cohorts. The underlying mechanisms of METTL3 in CRC were investigated by integrative m6 A sequencing, RNA sequencing, and ribosome profiling analyses. The efficacy of targeting METTL3 in CRC treatment was elucidated in CRC cell lines, patient-derived CRC organoids, and Mettl3-knockout mouse models.

方法：在多个大肠癌队列中研究METTL3的表达和临床意义。通过整合m6 A测序、RNA测序和核糖体印迹测序技术，研究了大肠癌中METTL3的潜在机制。在CRC细胞系、患者衍生的CRC类器官和METTL3敲除小鼠模型中阐明了靶向METTL3在CRC治疗中的疗效。

RESULTS: Using targeted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 dropout screening, we identified METTL3 as the top essential m6 A regulatory enzyme in CRC. METTL3 was overexpressed in 62.2% (79/127) and 88.0% METTL3 transgenic mouse models.

结果：使用靶向聚类规则间隔短回文重复序列（CRISPR）/Cas9缺失筛选，我们确定METTL3是大肠癌中最重要的m6A调节酶。METTL3在62.2%（79/127）和88.0%的METTL3转基因小鼠模型中过度表达。

CONCLUSIONS: METTL3 promotes CRC by activating the m6 A-GLUT1-mTORC1 axis. METTL3 is a promising therapeutic target for the treatment of CRC.

结论：METTL3通过激活m6 A-GLUT1-mTORC1轴促进CRC。METTL3是治疗大肠癌的一个有前景的治疗靶点。

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参考文献：

1.Chen H, Gao S, Liu W, et al. RNA m6A methyltransferase METTL3 facilitates colorectal cancer by activating m6A-GLUT1-mTORC1 axis and is a therapeutic target[J].

文献信息

标题	RNA N6-Methyladenosine Methyltransferase METTL3 Facilitates Colorectal Cancer by Activating the m6A-GLUT1-mTORC1 Axis and Is a Therapeutic Target
DOI	10.1053/j.gastro.2020.11.013
作者	Huarong Chen,Shanshan Gao,Weixin Liu,Chi-Chun Wong,Jianfeng Wu,Jingtong Wu,Dabin Liu,Hongyan Gou,Wei Kang,Jianning Zhai,Chuangen
期刊	Gastroenterology
页码	volume:160 issue:4 page:1284-1300.e16页
时间	2020-11-18
主题	Gastroenterology,Hepatology