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      CircRNAs in cancer metabolism: a review

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          Abstract

          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 references45

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis

            Abstract Background Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. Northern blotting, Sanger sequencing, antibody, and liquid chromatograph Tandem Mass Spectrometer were used to confirm the existence of circ-FBXW7 and its encoded protein in in two cell lines. Lentivirus-transfected stable U251 and U373 cells were used to assess the biological functions of the novel protein in vitro and in vivo (five mice per group). Clinical implications of circ-FBXW7 were assessed in 38 pathologically diagnosed glioblastoma samples and their paired periphery normal brain tissues by using quantitative polymerase chain reaction (two-sided log-rank test). Results Circ-FBXW7 is abundantly expressed in the normal human brain (reads per kilobase per million mapped reads [RPKM] = 9.31). The spanning junction open reading frame in circ-FBXW7 driven by internal ribosome entry site encodes a novel 21-kDa protein, which we termed FBXW7-185aa. Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes in vitro and in vivo. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P < .001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03). Conclusions Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer.
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              Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression.

              Metabolic reprogramming is widely observed during cancer development to confer cancer cells the ability to survive and proliferate, even under the stressed, such as nutrient-limiting, conditions. It is famously known that cancer cells favor the "Warburg effect", i.e., the enhanced glycolysis or aerobic glycolysis, even when the ambient oxygen supply is sufficient. In addition, deregulated anabolism/catabolism of fatty acids and amino acids, especially glutamine, serine and glycine, have been identified to function as metabolic regulators in supporting cancer cell growth. Furthermore, extensive crosstalks are being revealed between the deregulated metabolic network and cancer cell signaling. These exciting advancements have inspired new strategies for treating various malignancies by targeting cancer metabolism. Here we review recent findings related to the regulation of glucose, fatty acid and amino acid metabolism, their crosstalk, and relevant cancer therapy strategy.
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                Author and article information

                Contributors
                tongpeng_xu_njmu@163.com
                yongqian_shu@163.com
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                4 September 2019
                4 September 2019
                2019
                : 12
                : 90
                Affiliations
                [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
                Author information
                http://orcid.org/0000-0002-3034-685X
                Article
                776
                10.1186/s13045-019-0776-8
                6727394
                31484561
                9572d1b3-a37f-465c-9728-d48494a1b98f
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), 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 ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 July 2019
                : 16 August 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, 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 :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                cancer metabolism,circrnas,warburg effect,lipid metabolism,glutamine,ros
                Oncology & Radiotherapy
                cancer metabolism, circrnas, warburg effect, lipid metabolism, glutamine, ros

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