METTL3 介导的 MMP9 mRNA 的 N6-甲基腺苷修饰可促进结直肠癌的增殖和迁移。

IF 3.8 3区 医学 Q2 ONCOLOGY
Oncology reports Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI:10.3892/or.2024.8842
Jie Chen, Henglan Wu, Ting Zuo, Jianming Wu, Zhiheng Chen
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引用次数: 0

摘要

N6-甲基腺苷(m6A)是真核 mRNA 的主要化学修饰,由 RNA 甲基转移酶类甲基转移酶 3(METTL3)动态介导。然而,METTL3 及其相关的 m6A 修饰在结直肠肿瘤发生中的作用仍有待全面阐明。在本研究中,基于癌症数据库的生物信息学分析表明,METTL3表达和m6A水平在结直肠癌(CRC)中均上调,并与临床进展呈正相关。此外,在体外敲除和过表达 METTL3 会显著影响 CRC 细胞的活力、凋亡和迁移。同样,异种移植动物模型证实,METTL3 在体内促进了 CRC 的致瘤性。从机理上讲,METTL3介导的基质金属肽酶9(MMP9)mRNA的m6A修饰通过减少其降解促进了其在CRC中的表达。总之,本研究的结果表明,METTL3/MMP9 轴可作为一种治疗 CRC 的新型候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
METTL3‑mediated N6‑methyladenosine modification of MMP9 mRNA promotes colorectal cancer proliferation and migration.

N6‑methyladenosine (m6A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m6A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m6A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m6A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration in vitro. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity in vivo. Mechanistically, it was revealed that the m6A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.

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来源期刊
Oncology reports
Oncology reports 医学-肿瘤学
CiteScore
8.50
自引率
2.40%
发文量
187
审稿时长
3 months
期刊介绍: Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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