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TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development

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收录情况： ◇ SCIE

作者：
Chen Cong[1] * ; Chao Yinghui[2] * ; Zhang Chengcheng[1] ; Hu Wenyu[1] ; Huang Yapeng[1] ; Lv Yifan[3] ; Liu Bixia[1] ; Ji Ding[4] ; Liu Mingrui[1] ; Yang Baotong[5] ; Jiang Lujing[6] ; Liang Yaomin[1] ; Zhang Haiqing[1] ; Yuan Gang[7] ; Ying Xiaoling[1,5,*1] ; Ji Weidong[1] ;
单位： [1]Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China [2]Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China [3]Guangdong Key Laboratory of Urology, Department of Urology, Minimally Invasive Surgery Center, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510080, China [4]Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China [5]Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510080, China [6]Guangdong Provincial People’s Hospital, Guangzhou, 510080, China [7]Private Medical Service & Healthcare Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
出处：
DOI： 10.1016/j.canlet.2023.216246
ISSN：

摘要：
RNA modifications, including adenine methylation (m6A) of mRNA and guanine methylation (m7G) of tRNA, are crucial for the biological function of RNA. However, the mechanism underlying the translation of specific genes synergistically mediated by dual m6A/m7G RNA modifications in bladder cancer (BCa) remains unclear. We demonstrated that m6A methyltransferase METTL3-mediated programmable m6A modification of oncogene trophoblast cell surface protein 2 (TROP2) mRNA promoted its translation during malignant transformation of bladder epithelial cells. m7G methyltransferase METTL1 enhanced TROP2 translation by mediating m7G modification of certain tRNAs. TROP2 protein inhibition decreased the proliferation and invasion of BCa cells in vitro and in vivo. Moreover, synergistical knockout of METTL3/METTL1 inhibited BCa cell proliferation, migration, and invasion; however, TROP2 overexpression partially abrogated its effect. Furthermore, TROP2 expression was significantly positively correlated with the expression levels of METTL3 and METTL1 in BCa patients. Overall, our results revealed that METTL3/METTL1-mediated dual m6A/m7G RNA modifications enhanced TROP2 translation and promoted BCa development, indicating a novel RNA epigenetic mechanism in BCa.Copyright © 2023 Elsevier B.V. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China [grant number 82073047 and 82272995].
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
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出版当年[2021]版：
Q1 ONCOLOGY
最新[2024]版：
Q1 ONCOLOGY

影响因子： 最新[2024版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
共同第一作者：
通讯作者：
通讯机构： [1]Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China [5]Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510080, China [*1]Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510080, China.
推荐引用方式(GB/T 7714)：
Chen Cong,Chao Yinghui,Zhang Chengcheng,et al.TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development[J].CANCER LETTERS.2023,566:doi:10.1016/j.canlet.2023.216246.
APA：
Chen Cong,Chao Yinghui,Zhang Chengcheng,Hu Wenyu,Huang Yapeng...&Ji Weidong.(2023).TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development.CANCER LETTERS,566,
MLA：
Chen Cong,et al."TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development".CANCER LETTERS 566.(2023)

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