2. Academic Validation
  3. Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2

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

  • Nat Commun. 2020 Jun 22;11(1):3162. doi: 10.1038/s41467-020-16966-3.
Chunqing Wang  # 1,  Yongmei Li  # 2,  Shuai Yan  # 3,  Hao Wang 3 4,  Xianfeng Shao 3 5,  Mingming Xiao 1,  Baicai Yang 3 6,  Guoxuan Qin 7,  Ruirui Kong 8,  Ruibing Chen 9,  Ning Zhang 10 11
Affiliations

Affiliations

  • 1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, 300070, Tianjin, China.
  • 2 Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
  • 3 Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
  • 4 School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, China.
  • 5 Tianjin Medical University Eye Hospital, Eye Institute & School of Optometry and Ophthalmology, 300384, Tianjin, China.
  • 6 Department of Gynecology and Obstetrics, Jiaxing Maternity and Child Health Care Hospital, 314050, Jiaxing, China.
  • 7 School of Microelectronics, Tianjin University, 300072, Tianjin, China.
  • 8 Peking University First Hospital, Peking University Health Science Center, 100034, Beijing, China.
  • 9 School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, China. rbchen@tju.edu.cn.
  • 10 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, 300070, Tianjin, China. zhangning@bjmu.edu.cn.
  • 11 Peking University First Hospital, Peking University Health Science Center, 100034, Beijing, China. zhangning@bjmu.edu.cn.
  • # Contributed equally.
PMID: 32572027 DOI: 10.1038/s41467-020-16966-3
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.

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