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Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2

Author

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  • Chunqing Wang

    (Tianjin Medical University)

  • Yongmei Li

    (Tianjin Medical University)

  • Shuai Yan

    (Tianjin Medical University)

  • Hao Wang

    (Tianjin Medical University
    Tianjin University)

  • Xianfeng Shao

    (Tianjin Medical University
    Eye Institute & School of Optometry and Ophthalmology)

  • Mingming Xiao

    (Tianjin Medical University)

  • Baicai Yang

    (Tianjin Medical University
    Jiaxing Maternity and Child Health Care Hospital)

  • Guoxuan Qin

    (Tianjin University)

  • Ruirui Kong

    (Peking University Health Science Center)

  • Ruibing Chen

    (Tianjin University)

  • Ning Zhang

    (Tianjin Medical University
    Peking University Health Science Center)

Abstract

Interacting with proteins is a crucial way for long noncoding RNAs (lncRNAs) to exert their biological responses. Here we report a high throughput strategy to characterize lncRNA interacting proteins in vivo by combining tobramycin affinity purification and mass spectrometric analysis (TOBAP-MS). Using this method, we identify 140 candidate binding proteins for lncRNA highly upregulated in liver cancer (HULC). Intriguingly, HULC directly binds to two glycolytic enzymes, lactate dehydrogenase A (LDHA) and pyruvate kinase M2 (PKM2). Mechanistic study suggests that HULC functions as an adaptor molecule that enhances the binding of LDHA and PKM2 to fibroblast growth factor receptor type 1 (FGFR1), leading to elevated phosphorylation of these two enzymes and consequently promoting glycolysis. This study provides a convenient method to study lncRNA interactome in vivo and reveals a unique mechanism by which HULC promotes Warburg effect by orchestrating the enzymatic activities of glycolytic enzymes.

Suggested Citation

  • Chunqing Wang & Yongmei Li & Shuai Yan & Hao Wang & Xianfeng Shao & Mingming Xiao & Baicai Yang & Guoxuan Qin & Ruirui Kong & Ruibing Chen & Ning Zhang, 2020. "Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16966-3
    DOI: 10.1038/s41467-020-16966-3
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    Cited by:

    1. Xueman Chen & Rong Luo & Yunmei Zhang & Shuying Ye & Xin Zeng & Jiang Liu & Di Huang & Yujie Liu & Qiang Liu & Man-Li Luo & Erwei Song, 2022. "Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Alastair G. Kerr & Zuoneng Wang & Na Wang & Kelvin H. M. Kwok & Jutta Jalkanen & Alison Ludzki & Simon Lecoutre & Dominique Langin & Martin O. Bergo & Ingrid Dahlman & Carsten Mim & Peter Arner & Hui , 2022. "The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Joel I. Perez-Perri & Dunja Ferring-Appel & Ina Huppertz & Thomas Schwarzl & Sudeep Sahadevan & Frank Stein & Mandy Rettel & Bruno Galy & Matthias W. Hentze, 2023. "The RNA-binding protein landscapes differ between mammalian organs and cultured cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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