title: LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress.
abstract: Long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cellular processes. However, the potential involvement of lncRNAs in kinase signalling remains largely unknown. AMP-activated protein kinase (AMPK) acts as a critical sensor of cellular energy status. Here we show that the lncRNA NBR2 (neighbour of BRCA1 gene 2) is induced by the LKB1-AMPK pathway under energy stress. On energy stress, NBR2 in turn interacts with AMPK and promotes AMPK kinase activity, thus forming a feed-forward loop to potentiate AMPK activation during energy stress. Depletion of NBR2 attenuates energy-stress-induced AMPK activation, resulting in unchecked cell cycling, altered apoptosis/autophagy response, and increased tumour development in vivo. NBR2 is downregulated and its low expression correlates with poor clinical outcomes in some human cancers. Together, the results of our study uncover a mechanism coupling lncRNAs with metabolic stress response, and provides a broad framework to understand further the regulation of kinase signalling by lncRNAs.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas 77030, USA.
authors.forename: Leng
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Jiexin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Program of Genes and Development, and Program of Cancer Biology, The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Program of Genes and Development, and Program of Cancer Biology, The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Program of Genes and Development, and Program of Cancer Biology, The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.|Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan.
authors.forename: Hui-Kuan
authors.initials: HK
authors.lastname: Lin
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Han
authors.identifier: http://orcid.org/0000-0001-7633-286X
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Program of Genes and Development, and Program of Cancer Biology, The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Boyi
authors.initials: B
authors.lastname: Gan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014183:Transplantation, Heterologous
chemical_list: C107422:NBR2 lncRNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases