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LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism

Author

Listed:
  • Xin-yu He

    (Zhejiang University
    Zhejiang University
    Key Laboratory for Cell and Gene Engineering of Zhejiang Province)

  • Xiao Fan

    (Zhejiang University
    Zhejiang University
    Key Laboratory for Cell and Gene Engineering of Zhejiang Province)

  • Lei Qu

    (Zhejiang University
    Zhejiang University
    Key Laboratory for Cell and Gene Engineering of Zhejiang Province)

  • Xiang Wang

    (the First People’s Hospital of Huzhou)

  • Li Jiang

    (Zhejiang University School of Medicine)

  • Ling-jie Sang

    (Zhejiang University)

  • Cheng-yu Shi

    (Zhejiang University)

  • Siyi Lin

    (Zhejiang University)

  • Jie-cheng Yang

    (Zhejiang University)

  • Zuo-zhen Yang

    (Zhejiang University)

  • Kai Lei

    (Zhejiang University)

  • Jun-hong Li

    (Zhejiang University)

  • Huai-qiang Ju

    (Collaborative Innovation Center for Cancer Medicine)

  • Qingfeng Yan

    (Zhejiang University)

  • Jian Liu

    (Zhejiang University School of Medicine, Zhejiang University
    Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University)

  • Fudi Wang

    (Zhejiang University School of Medicine)

  • Jianzhong Shao

    (Zhejiang University)

  • Yan Xiong

    (Zhejiang University)

  • Wenqi Wang

    (University of California, Irvine)

  • Aifu Lin

    (Zhejiang University
    Zhejiang University
    Key Laboratory for Cell and Gene Engineering of Zhejiang Province
    The 4th Affiliated Hospital of Zhejiang University School of Medicine)

Abstract

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.

Suggested Citation

  • Xin-yu He & Xiao Fan & Lei Qu & Xiang Wang & Li Jiang & Ling-jie Sang & Cheng-yu Shi & Siyi Lin & Jie-cheng Yang & Zuo-zhen Yang & Kai Lei & Jun-hong Li & Huai-qiang Ju & Qingfeng Yan & Jian Liu & Fud, 2023. "LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37871-5
    DOI: 10.1038/s41467-023-37871-5
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    References listed on IDEAS

    as
    1. Jiao Wu & Alexander M. Minikes & Minghui Gao & Huijie Bian & Yong Li & Brent R. Stockwell & Zhi-Nan Chen & Xuejun Jiang, 2019. "Publisher Correction: Intercellular interaction dictates cancer cell ferroptosis via NF2–YAP signalling," Nature, Nature, vol. 572(7770), pages 20-20, August.
    2. Ya-fang Wang & Jie Zhang & Yi Su & Yan-yan Shen & Dong-xian Jiang & Ying-yong Hou & Mei-yu Geng & Jian Ding & Yi Chen, 2017. "G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Zhipeng Meng & Yunjiang Qiu & Kimberly C. Lin & Aditya Kumar & Jesse K. Placone & Cao Fang & Kuei-Chun Wang & Shicong Lu & Margaret Pan & Audrey W. Hong & Toshiro Moroishi & Min Luo & Steven W. Plouff, 2018. "RAP2 mediates mechanoresponses of the Hippo pathway," Nature, Nature, vol. 560(7720), pages 655-660, August.
    4. Kei Saotome & Swetha E. Murthy & Jennifer M. Kefauver & Tess Whitwam & Ardem Patapoutian & Andrew B. Ward, 2018. "Structure of the mechanically activated ion channel Piezo1," Nature, Nature, vol. 554(7693), pages 481-486, February.
    5. Dana Elster & Marie Tollot & Karin Schlegelmilch & Alessandro Ori & Andreas Rosenwald & Erik Sahai & Björn von Eyss, 2018. "TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    6. Jiao Wu & Alexander M. Minikes & Minghui Gao & Huijie Bian & Yong Li & Brent R. Stockwell & Zhi-Nan Chen & Xuejun Jiang, 2019. "Intercellular interaction dictates cancer cell ferroptosis via NF2–YAP signalling," Nature, Nature, vol. 572(7769), pages 402-406, August.
    7. Pearl Lee & Dania Malik & Nicholas Perkons & Peiwei Huangyang & Sanika Khare & Seth Rhoades & Yao-Yu Gong & Michelle Burrows & Jennifer M. Finan & Itzhak Nissim & Terence P. F. Gade & Aalim M. Weljie , 2020. "Targeting glutamine metabolism slows soft tissue sarcoma growth," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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