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      LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer

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          Abstract

          Altered metabolism is a hallmark of cancer, and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors. It is well recognized that long noncoding RNAs (lncRNAs) regulate energy metabolism in cancer. However, lncRNA‐mediated posttranslational modifications and metabolic reprogramming are unclear at present. In this review, we summarized the current understanding of the interactions between the alterations in cancer‐associated energy metabolism and the lncRNA‐mediated posttranslational modifications of metabolic enzymes, transcription factors, and other proteins involved in metabolic pathways. In addition, we discuss the mechanisms through which these interactions contribute to tumor initiation and progression, and the key roles and clinical significance of functional lncRNAs. We believe that an in‐depth understanding of lncRNA‐mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.

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          Most cited references90

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          The Emerging Hallmarks of Cancer Metabolism.

          Tumorigenesis is dependent on the reprogramming of cellular metabolism as both direct and indirect consequence of oncogenic mutations. A common feature of cancer cell metabolism is the ability to acquire necessary nutrients from a frequently nutrient-poor environment and utilize these nutrients to both maintain viability and build new biomass. The alterations in intracellular and extracellular metabolites that can accompany cancer-associated metabolic reprogramming have profound effects on gene expression, cellular differentiation, and the tumor microenvironment. In this Perspective, we have organized known cancer-associated metabolic changes into six hallmarks: (1) deregulated uptake of glucose and amino acids, (2) use of opportunistic modes of nutrient acquisition, (3) use of glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, (4) increased demand for nitrogen, (5) alterations in metabolite-driven gene regulation, and (6) metabolic interactions with the microenvironment. While few tumors display all six hallmarks, most display several. The specific hallmarks exhibited by an individual tumor may ultimately contribute to better tumor classification and aid in directing treatment.
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            Functional Classification and Experimental Dissection of Long Noncoding RNAs

            Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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              AMPK: guardian of metabolism and mitochondrial homeostasis.

              Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.
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                Author and article information

                Contributors
                xurh@sysucc.org.cn
                juhq@sysucc.org.cn
                Journal
                Cancer Commun (Lond)
                Cancer Commun (Lond)
                10.1002/(ISSN)2523-3548
                CAC2
                Cancer Communications
                John Wiley and Sons Inc. (Hoboken )
                2523-3548
                29 October 2020
                February 2021
                : 41
                : 2 ( doiID: 10.1002/cac2.v41.2 )
                : 109-120
                Affiliations
                [ 1 ] Department of Medical Oncology, Sun Yat‐sen University Cancer Center; State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou Guangdong 510060 P. R. China
                [ 2 ] Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical Sciences Guangzhou Guangdong 510060 P. R. China
                Author notes
                [*] [* ] Correspondence

                Huai‐Qiang Ju and Rui‐Hua Xu, Department of Medical Oncology, Sun Yat‐sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, P. R. China.

                Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, Guangdong, P. R. China.

                Email: juhq@ 123456sysucc.org.cn ; xurh@ 123456sysucc.org.cn

                [*]

                These authors contributed equally to this work.

                Article
                CAC212108
                10.1002/cac2.12108
                7896749
                33119215
                7d993143-b2fc-4890-a7f7-0b23aa367fa0
                © 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat‐sen University Cancer Center

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 20 July 2020
                : 06 September 2020
                : 19 October 2020
                Page count
                Figures: 3, Tables: 0, Pages: 12, Words: 6847
                Funding
                Funded by: National Key R&D Program of China
                Award ID: 2018YFC1313304
                Award ID: 2018YFC1313300
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 82073112
                Award ID: 82022052
                Award ID: 81871951
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:20.02.2021

                cancer metabolism,enzyme,long noncoding rna,metabolic reprogramming,posttranslational modification

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