Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner.
Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner.
复制标题
甲基转移酶 3 通过以 m6A 依赖性方式增强组织蛋白酶 L mRNA 稳定性来促进宫颈癌转移
作者：
N6-甲基腺苷（m6 A）是真核细胞中高度丰富的RNA修饰。甲基转移酶样3（Methyltransferase‐like 3，缩写为L3）是m6 A甲基转移酶复合物中的一种主要蛋白，在许多恶性肿瘤中发挥重要作用，但其在宫颈癌转移中的作用仍不确定。在这里，我们发现胃L3在宫颈癌组织中显著上调，并且其上调与宫颈癌患者的不良预后相关。敲除胃L3显著降低宫颈癌细胞的迁移和侵袭。相反，在体外和体内，胃L3过表达显著促进宫颈癌细胞的转移。此外，胃L3介导组织蛋白酶L（CTSL）mRNA在5′-UTR处的m6 A修饰，并且m6 A阅读蛋白胰岛素样生长因子2 mRNA结合蛋白2（IGF 2BP 2）结合到m6 A位点并增强CTSL mRNA的稳定性。我们的结果表明，CTSL 3通过m6 A-IGF 2 BP 2-依赖性机制增强CTSL mRNA的稳定性，从而促进宫颈癌细胞转移。这些发现提供了一种新的m6 A修饰模式参与宫颈癌发展的见解。我们发现，子宫颈癌中的胃L3/CTSL/IGF 2BP 2轴过度激活，导致子宫颈癌细胞的转移能力升高。我们的数据表明，胃L3在宫颈癌细胞的迁移和侵袭中起致癌作用，并为开发治疗宫颈癌的治疗策略提供了见解。
N6‐methyladenosine (m6A) is a highly abundant RNA modification in eukaryotic cells. Methyltransferase‐like 3 (METTL3), a major protein in the m6A methyltransferase complex, plays important roles in many malignancies, but its role in cervical cancer metastasis remains uncertain. Here, we found that METTL3 was significantly upregulated in cervical cancer tissue, and its upregulation was associated with a poor prognosis in cervical cancer patients. Knockdown of METTL3 significantly reduced cervical cancer cell migration and invasion. Conversely, METTL3 overexpression markedly promoted cervical cancer cell metastasis in vitro and in vivo. Furthermore, METTL3 mediated the m6A modification of cathepsin L (CTSL) mRNA at the 5′‐UTR, and the m6A reader protein insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A‐IGF2BP2‐dependent mechanism, thereby promoting cervical cancer cell metastasis. These findings provide insights into a novel m6A modification pattern involved in cervical cancer development. We found that the METTL3/CTSL/IGF2BP2 axis is overactivated in cervical cancer, resulting in elevated metastasis ability of cervical cancer cells. Our data indicate that METTL3 plays an oncogenic role in the migration and invasion of cervical cancer cells and provide insights for developing therapeutic strategies to treat cervical cancers.
登录
查看更多内容
影响因子：
4.3
作者：
Gocheva, Vasilena;Joyce, Johanna A.
通讯作者：
Joyce, Johanna A.
影响因子：
4.9
作者：
Liang X;Zhang Z;Wang L;Zhang S;Ren L;Li S;Xu J;Lv S
通讯作者：
Lv S
ITGA6 mRNA N-6-甲基腺苷修饰促进膀胱癌的发生和进展
影响因子：
11.1
作者：
Jin, Huan;Ying, Xiaoling;Ji, Weidong
通讯作者：
Ji, Weidong
慢性髓样白血病中组织蛋白酶L表达的表观遗传调节。
影响因子：
5.3
作者：
Samaiya M;Bakhshi S;Shukla AA;Kumar L;Chauhan SS
通讯作者：
Chauhan SS
DOI：
10.1016/j.gpb.2017.03.002
发表时间：
2017-06
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
Batista PJ
通讯作者：
Batista PJ