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CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes

Author

Listed:
  • Yanfen Zheng

    (Sun Yat-sen University Cancer Center)

  • Xingyang Li

    (Sun Yat-sen University Cancer Center)

  • Shuang Deng

    (Sun Yat-sen University Cancer Center)

  • Hongzhe Zhao

    (Sun Yat-sen University Cancer Center)

  • Ying Ye

    (Sun Yat-sen University Cancer Center)

  • Shaoping Zhang

    (Sun Yat-sen University Cancer Center)

  • Xudong Huang

    (Sun Yat-sen University Cancer Center)

  • Ruihong Bai

    (Sun Yat-sen University Cancer Center)

  • Lisha Zhuang

    (Sun Yat-sen University Cancer Center)

  • Quanbo Zhou

    (Sun Yat-sen University)

  • Mei Li

    (Sun Yat-sen University Cancer Center)

  • Jiachun Su

    (Sun Yat-sen University Cancer Center)

  • Rui Li

    (Sun Yat-sen University Cancer Center)

  • Xiaoqiong Bao

    (Sun Yat-sen University Cancer Center)

  • Lingxing Zeng

    (Sun Yat-sen University Cancer Center)

  • Rufu Chen

    (Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences)

  • Jian Zheng

    (Sun Yat-sen University Cancer Center
    Nanjing Medical University
    Affiliated Cancer Hospital and Institute of Guangzhou Medical University)

  • Dongxin Lin

    (Sun Yat-sen University Cancer Center
    Nanjing Medical University
    National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Chuan He

    (The University of Chicago
    The University of Chicago
    The University of Chicago)

  • Jialiang Zhang

    (Sun Yat-sen University Cancer Center)

  • Zhixiang Zuo

    (Sun Yat-sen University Cancer Center)

Abstract

N6-methyladenosine (m6A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m6A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m6A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m6A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m6A regulator CSTF2 that co-transcriptionally regulates m6A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m6As have positive effects on the RNA level of host genes, and CSTF2-regulated m6As are mainly recognized by IGF2BP2, an m6A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.

Suggested Citation

  • Yanfen Zheng & Xingyang Li & Shuang Deng & Hongzhe Zhao & Ying Ye & Shaoping Zhang & Xudong Huang & Ruihong Bai & Lisha Zhuang & Quanbo Zhou & Mei Li & Jiachun Su & Rui Li & Xiaoqiong Bao & Lingxing Z, 2023. "CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41861-y
    DOI: 10.1038/s41467-023-41861-y
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    References listed on IDEAS

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    1. Jialiang Zhang & Ruihong Bai & Mei Li & Huilin Ye & Chen Wu & Chengfeng Wang & Shengping Li & Liping Tan & Dongmei Mai & Guolin Li & Ling Pan & Yanfen Zheng & Jiachun Su & Ying Ye & Zhiqiang Fu & Shan, 2019. "Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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