IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29125-7.html
   My bibliography  Save this article

N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis

Author

Listed:
  • Hui Han

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Chunlong Yang

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Jieyi Ma

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Shuishen Zhang

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Siyi Zheng

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Rongsong Ling

    (Institute for Advanced Study, Shenzhen University)

  • Kaiyu Sun

    (The First Affiliated Hospital of Sun Yat-sen University)

  • Siyao Guo

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Boxuan Huang

    (Institute for Advanced Study, Shenzhen University)

  • Yu Liang

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Lu Wang

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Shuang Chen

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Zhaoyu Wang

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Wei Wei

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Ying Huang

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Hao Peng

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University)

  • Yi-Zhou Jiang

    (Institute for Advanced Study, Shenzhen University)

  • Junho Choe

    (College of Natural Sciences, Hanyang University
    Research Institute for Natural Sciences, Hanyang University)

  • Shuibin Lin

    (Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University
    State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center)

Abstract

Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment.

Suggested Citation

  • Hui Han & Chunlong Yang & Jieyi Ma & Shuishen Zhang & Siyi Zheng & Rongsong Ling & Kaiyu Sun & Siyao Guo & Boxuan Huang & Yu Liang & Lu Wang & Shuang Chen & Zhaoyu Wang & Wei Wei & Ying Huang & Hao Pe, 2022. "N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29125-7
    DOI: 10.1038/s41467-022-29125-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29125-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29125-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Junho Choe & Shuibin Lin & Wencai Zhang & Qi Liu & Longfei Wang & Julia Ramirez-Moya & Peng Du & Wantae Kim & Shaojun Tang & Piotr Sliz & Pilar Santisteban & Rani E. George & William G. Richards & Kwo, 2018. "mRNA circularization by METTL3–eIF3h enhances translation and promotes oncogenesis," Nature, Nature, vol. 561(7724), pages 556-560, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Qiaoqiao Zhang & Kai Deng & Mengyou Liu & Shengye Yang & Wei Xu & Tong Feng & Minwen Jie & Zhiming Liu & Xiao Sheng & Haiyang Chen & Hao Jiang, 2023. "Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Huilin Jin & Xiaoling Huang & Qihao Pan & Ning Ma & Xiaoshan Xie & Yue Wei & Fenghai Yu & Weijie Wen & Boyu Zhang & Peng Zhang & Xijie Chen & Jie Wang & Ran-yi Liu & Junzhong Lin & Xiangqi Meng & Mong, 2024. "The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Xin Yang & Robinson Triboulet & Qi Liu & Erdem Sendinc & Richard I. Gregory, 2022. "Exon junction complex shapes the m6A epitranscriptome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Xinzhi Li & Bingchuan Yuan & Min Lu & Yuqin Wang & Na Ding & Chunhong Liu & Ming Gao & Zhicheng Yao & Shiyan Zhang & Yujun Zhao & Liwei Xie & Zheng Chen, 2021. "The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Yuanpei Li & Xiaoniu He & Xiao Lu & Zhicheng Gong & Qing Li & Lei Zhang & Ronghui Yang & Chengyi Wu & Jialiang Huang & Jiancheng Ding & Yaohui He & Wen Liu & Ceshi Chen & Bin Cao & Dawang Zhou & Yufen, 2022. "METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    6. WeiChao Hao & MeiJuan Dian & Ying Zhou & QiuLing Zhong & WenQian Pang & ZiJian Li & YaYan Zhao & JiaCheng Ma & XiaoLin Lin & RenRu Luo & YongLong Li & JunShuang Jia & HongFen Shen & ShiHao Huang & Gua, 2022. "Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29125-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.