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Zhenqiang Sun^1,2,3, Yanxin Xu^4,5,6, Chaohua Si^7,8

¹Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. fccsunzq@zzu.edu.cn.

Molecular cancer

|August 30, 2024

概括

METTL1酶通过m7G修改circRNAs,通过稳定circKDM1A和激活AKT通路来增强结直肠癌 (CRC) 的进展. 这项研究揭示了CRC开发中的一个关键机制.

科学领域:

分子生物学分子生物学
在瘤学瘤学.
在RNA生物学,RNA生物学.

背景情况:

循环RNAs (circRNAs) 与结直肠癌 (CRC) 有关,但驱动其异常表达的机制尚不清楚.
越来越多地认识到RNA修饰,如N6-甲基氨酸 (m6A),它们在基因调节和癌症中的作用.

研究的目的:

为了研究m7GRNA修饰在结直肠癌中的circRNAs中的作用.
阐明METTL1影响circRNA稳定性和CRC进展的机制.
确定由METTL1调节的特定circRNA及其对CRC的下游影响.

主要方法:

来自CRC样本的circRNAs中的m7G修饰丰富的分析.
识别METTL1作为m7G甲基转移酶用于circRNAs,GG动机优先.
功能性测试 (体外和体内) 评估circKDM1A及其m7G修饰对CRC细胞增殖,入侵和迁移的影响.
西部涂抹和qRT-PCR检查AKT通路和PDK1表达的激活.

主要成果:

m7G修饰在CRC中的某些circRNA中得到丰富,由METTL1催化,偏好GG动机.
METTL1通过m7G修饰稳定circKDM1A,促进CRC进展,增强扩散,入侵和迁移.
CircKDM1A通过上调PDK1来激活AKT通路,从而促进CRC的进展;在m7G位点突变时,这种效果会减弱.

结论:

通过METTL1介导的m7G修饰circRNAs是结直肠癌进展的关键机制.
已识别的circKDM1A通过m7G修饰稳定并激活AKT/PDK1通路,在CRC中充当瘤基因.
这项研究揭示了一个新的调节轴,涉及METTL1,m7G修饰的circRNAs,以及在CRC发病过程中的AKT途径.

关键词:

在 AKT 路径上.大肠直肠癌 (CRC) 是一种癌症.修改M7G的修改方法环RNA 环RNA 是一个环RNA.

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