2. Academic Validation
  3. N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression

N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression

  • Mol Cell. 2021 Aug 19;81(16):3339-3355.e8. doi: 10.1016/j.molcel.2021.07.003.
Zihao Dai 1,  Haining Liu 1,  Junbin Liao 1,  Cheng Huang 2,  Xiaoxue Ren 3,  Wanjie Zhu 3,  Shenghua Zhu 3,  Baogang Peng 1,  Shaoqiang Li 1,  Jiaming Lai 4,  Lijian Liang 1,  Lixia Xu 5,  Sui Peng 6,  Shuibin Lin 7,  Ming Kuang 8
Affiliations

Affiliations

  • 1 Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 2 Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 3 Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 4 Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 5 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 6 Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
  • 7 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China. Electronic address: linshb6@mail.sysu.edu.cn.
  • 8 Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China; Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China. Electronic address: kuangm@mail.sysu.edu.cn.
PMID: 34352206 DOI: 10.1016/j.molcel.2021.07.003
Abstract

Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate Cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and Cancer progression.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z