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Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression

Author

Listed:
  • Jialiang Zhang

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Ruihong Bai

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Mei Li

    (Sun Yat-sen University Cancer Center)

  • Huilin Ye

    (Sun Yat-sen University)

  • Chen Wu

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Chengfeng Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Shengping Li

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Liping Tan

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Dongmei Mai

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Guolin Li

    (Sun Yat-sen University)

  • Ling Pan

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Yanfen Zheng

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Jiachun Su

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Ying Ye

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Zhiqiang Fu

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Shangyou Zheng

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Zhixiang Zuo

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Zexian Liu

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Qi Zhao

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Xu Che

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dan Xie

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Weihua Jia

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Mu-Sheng Zeng

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Wen Tan

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Rufu Chen

    (Sun Yat-sen University)

  • Rui-Hua Xu

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Jian Zheng

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Dongxin Lin

    (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

N6-methyladenosine (m6A) modification is an important mechanism in miRNA processing and maturation, but the role of its aberrant regulation in human diseases remained unclear. Here, we demonstrate that oncogenic primary microRNA-25 (miR-25) in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced m6A modification that is mediated by NF-κB associated protein (NKAP). This modification is catalyzed by overexpressed methyltransferase-like 3 (METTL3) due to hypomethylation of the METTL3 promoter also caused by CSC. Mature miR-25, miR-25-3p, suppresses PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), resulting in the activation of oncogenic AKT-p70S6K signaling, which provokes malignant phenotypes of pancreatic cancer cells. High levels of miR-25-3p are detected in smokers and in pancreatic cancers tissues that are correlated with poor prognosis of pancreatic cancer patients. These results collectively indicate that cigarette smoke-induced miR-25-3p excessive maturation via m6A modification promotes the development and progression of pancreatic cancer.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09712-x
    DOI: 10.1038/s41467-019-09712-x
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    Cited by:

    1. Ya′nan Zhu & Jing He & Jiawen Wang & Wei Guo & Hongran Liu & Zhuoran Song & Le Kang, 2024. "Parental experiences orchestrate locust egg hatching synchrony by regulating nuclear export of precursor miRNA," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. 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.

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