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      CircRNAs in cancer metabolism: a review

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          Altered energy metabolism is a hallmark of tumors aiming at supplying necessary nutrients for tumorigenesis and development. These redirected metabolic pathways associated with carbohydrate, lipid and amino acid are orchestrated not only by carcinogenic proteins but by non-coding RNAs. Among them, circular RNA (circRNA), as a kind of novel identified non-coding RNAs, has become the focus of attention. Through binding with corresponding microRNAs or directly contacting proteins, circRNA plays a primarily important role in regulating cellular metabolism. Herein, we analyze the emerging findings and select circRNAs contributing to mutant glycolysis, lipogenesis and lipolysis, glutam inolysis, and oxidative respiration to deepen the understanding about the cancer metabolic regulatory network. In addition, we also discuss the possibility of circRNAs exerting their functions via exosomes and cancer stem cells. Owing to their unique structures and wide impacts, circRNAs may help reap huge fruits in developing clinical treatments targeting cancer metabolism.

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          Most cited references 82

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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             O WARBURG (1956)
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              Circular RNAs are a large class of animal RNAs with regulatory potency.

              Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

                Author and article information

                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                4 September 2019
                4 September 2019
                : 12
                [1 ]ISNI 0000 0004 1799 0784, GRID grid.412676.0, Department of Oncology, , First Affiliated Hospital of Nanjing Medical University, ; #300 Guangzhou Road, Nanjing, 210029 China
                [2 ]GRID grid.268415.c, Department of Pathology, , The Affiliated Hospital of Yangzhou University, ; Yangzhou, 225000 China
                [3 ]GRID grid.452247.2, Cancer Institute, , The Affiliated People’s Hospital of Jiangsu University, ; Zhenjiang, 212002 China
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

                Funded by: FundRef, National Natural Science Foundation of China;
                Award ID: 81672896
                Award ID: 81672071
                Award Recipient :
                Funded by: Natural Science Foundation of Jiangsu Province for Youth
                Award ID: BK20161066
                Award Recipient :
                Funded by: the National Key Research and Development Program
                Award ID: ZDZX2017ZL-01
                Award Recipient :
                Funded by: Jiangsu provincial key R&D special Fund
                Award ID: BE2015666
                Award Recipient :
                Funded by: Jiangsu Innovative team leading talent fund
                Award ID: CXTDC2016006
                Award Recipient :
                Funded by: Jiangsu Natural Science Foundation
                Award ID: BK20171304
                Award Recipient :
                Funded by: Natural Science Foundation of Jiangsu Provincial Department of Education
                Award ID: 17KJB320007
                Award Recipient :
                Funded by: Csco-Hawson Cancer Research Fund
                Award ID: Y-HS2017-032
                Award Recipient :
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                © The Author(s) 2019

                Oncology & Radiotherapy

                cancer metabolism, circrnas, warburg effect, lipid metabolism, glutamine, ros


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