METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m(7)G-modified miR-760-dependent manner.
METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m(7)G-modified miR-760-dependent manner.
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METTL1通过m7G修饰的miR-760依赖性方式降解ATF3 mRNA来驱动膀胱癌的肿瘤进展
DOI：
10.1038/s41420-022-01236-6
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发表时间：
2022-11-17
影响因子：
7
通讯作者：
Li, Gonghui
中科院分区：
文献类型：
--
作者：
Xie, Haiyun;Wang, Mingchao;Yu, Haifeng;Wang, Huan;Ding, Lifeng;Wang, Ruyue;Luo, Wenqin;Lu, Zeyi;Zheng, Qiming;Ren, Liangliang;Zhou, Zhenwei;Su, Wenjing;Xia, Liqun;Li, Gonghui
7-甲基鸟苷（m7G）修饰最近被发现保守地存在于mRNA帽外的RNA内部位置，并介导各种RNA代谢。作为m7G修饰的核心转甲基化酶，METTL1已在某些人类癌症中被报道。然而，内部m7G在miRNAs及其核心作者METTL1在膀胱癌（BCa）中的作用仍有待阐明。在这里，我们证明了METTL1对于BCa体外和体内的增殖和转移是必不可少的。通过结合miRNA测序、m7G甲基化RNA免疫沉淀（MeRIP）和RIP，我们发现METTL1以m7G依赖的方式促进了miR-760的加工。转录测序表明METTL1间接降解miR-760介导的肿瘤抑制因子ATF3 mRNA。总之，我们得出了由METTL1/m7G/miR-760/ATF3组成的调节轴在调节BCa进展中，并为BCa提供了潜在的治疗靶点。
7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.
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影响因子：
7.5
作者：
Han, Ming-li;Wang, Fang;Wang, Yi-meng
通讯作者：
Wang, Yi-meng
影响因子：
4.5
作者：
Alexandrov, A;Martzen, MR;Phizicky, EM
通讯作者：
Phizicky, EM
影响因子：
5.2
作者：
De Paolis V;Lorefice E;Orecchini E;Carissimi C;Laudadio I;Fulci V
通讯作者：
Fulci V
影响因子：
23.9
作者：
Batista, Pedro J.;Molinie, Benoit;Wang, Jinkai;Qu, Kun;Zhang, Jiajing;Li, Lingjie;Bouley, Donna M.;Lujan, Ernesto;Haddad, Bahareh;Daneshvar, Kaveh;Carter, Ava C.;Flynn, Ryan A.;Zhou, Chan;Lim, Kok-Seong;Dedon, Peter;Wernig, Marius;Mullen, Alan C.;Xing, Yi;Giallourakis, Cosmas C.;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
捕获新转录 RNA 的相互作用组
影响因子：
48
作者：
Bao X;Guo X;Yin M;Tariq M;Lai Y;Kanwal S;Zhou J;Li N;Lv Y;Pulido-Quetglas C;Wang X;Ji L;Khan MJ;Zhu X;Luo Z;Shao C;Lim DH;Liu X;Li N;Wang W;He M;Liu YL;Ward C;Wang T;Zhang G;Wang D;Yang J;Chen Y;Zhang C;Jauch R;Yang YG;Wang Y;Qin B;Anko ML;Hutchins AP;Sun H;Wang H;Fu XD;Zhang B;Esteban MA
通讯作者：
Esteban MA