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      Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

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          Abstract

          As the standard treatments for cancer, chemotherapy and radiotherapy have been widely applied to clinical practice worldwide. However, the resistance to cancer therapies is a major challenge in clinics and scientific research, resulting in tumor recurrence and metastasis. The mechanisms of therapy resistance are complicated and result from multiple factors. Among them, non-coding RNAs (ncRNAs), along with their modifiers, have been investigated to play key roles in regulating tumor development and mediating therapy resistance within various cancers, such as hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, etc. In this review, we attempt to elucidate the mechanisms underlying ncRNA/modifier-modulated resistance to chemotherapy and radiotherapy, providing some therapeutic potential points for future cancer treatment.

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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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            Natural RNA circles function as efficient microRNA sponges.

            MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
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              The functions of animal microRNAs.

              MicroRNAs (miRNAs) are small RNAs that regulate the expression of complementary messenger RNAs. Hundreds of miRNA genes have been found in diverse animals, and many of these are phylogenetically conserved. With miRNA roles identified in developmental timing, cell death, cell proliferation, haematopoiesis and patterning of the nervous system, evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
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                Author and article information

                Contributors
                shuangliu2016@csu.edu.cn
                xdsh96@21cn.com
                taoyong@csu.edu.cn
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                2 March 2020
                2 March 2020
                2020
                : 19
                : 47
                Affiliations
                [1 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, School of Basic Medicine, , Central South University, ; Changsha, 410078 Hunan China
                [2 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Cardiovascular Medicine, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [3 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Cardiovascular Medicine, Third Xiangya Hospital, , Central South University, ; Changsha, 410013 Hunan China
                [4 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Neurosurgery, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [5 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Geriatrics, Third Xiangya Hospital, , Central South University, ; Changsha, 410013 Hunan China
                [6 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Cardiovascular Surgery, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [7 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [8 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute, , Central South University, ; Changsha, 410078 Hunan China
                [9 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, Second Xiangya Hospital, , Central South University, ; Changsha, 410011 China
                Article
                1171
                10.1186/s12943-020-01171-z
                7050132
                32122355
                0169ad25-1bb0-4b70-8391-dac02e62c8d3
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 18 December 2019
                : 24 February 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81672991
                Award ID: 81874139
                Award ID: 81672787
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100012166, National Basic Research Program of China (973 Program);
                Award ID: 2015CB553903
                Award Recipient :
                Funded by: Hunan Provincial Key Area R&D Programmes
                Award ID: 2019SK2253
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                ncrnas,rna modifiers,chemoresistance,radioresistance
                Oncology & Radiotherapy
                ncrnas, rna modifiers, chemoresistance, radioresistance

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