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      Significance of alternative splicing in cancer cells

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          Abstract

          Objective

          Alternative splicing can generate various structural and functional protein isoforms. Recently, accumulating evidence shows a relationship between alternative splicing and cancer. Cancer is a complex and chronic disease that involves malignant transformation. In this review, we consider alternative splicing events in relation to the hallmarks of cancer cells, and discuss current therapies to treat cancer-related to alternative splicing.

          Data sources

          Data cited in this article are from the PubMed and Embase database, primarily focusing on research published from 2000 to 2018.

          Study selection

          Articles were selected with the search terms “alternative splicing,” “cancer cell,” “tumor microenvironment,” and “therapy.”

          Results

          Alternative splicing plays an important role in tumorigenesis, development, and escape from cell death. Taking this trait of cancer cells into consideration will allow more definite diagnoses of cancer, and allow the development of more effective medicines to intervene in cancer that could focus on controlling alternative splicing or competitively binding to the final products.

          Conclusions

          Alternative splicing is common in cancer cells. Consideration of alternative splicing may allow different strategies for cancer therapy or the identification of novel biomarkers for cancer diagnosis.

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          Most cited references76

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          Alternative splicing: new insights from global analyses.

          Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation of proteomic and functional diversity in metazoan organisms. Efforts are now being directed at establishing the full repertoire of functionally relevant transcript variants generated by alternative splicing, the specific roles of such variants in normal and disease physiology, and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions. Recent progress in these areas is summarized in this review.
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            Revisiting the hallmarks of cancer.

            The hallmarks of cancer described by Hanahan and Weinberg have proved seminal in our understanding of cancer's common traits and in rational drug design. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
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              The Functional Impact of Alternative Splicing in Cancer

              Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers).
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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CM9
                Chinese Medical Journal
                Wolters Kluwer Health
                0366-6999
                2542-5641
                20 January 2020
                20 January 2020
                : 133
                : 2
                : 221-228
                Affiliations
                Department of Geriatrics, Peking University First Hospital, Peking University, Beijing 100034, China.
                Author notes
                Correspondence to: Dr. Xin-Min Liu, Department of Geriatrics, Peking University First Hospital, Beijing 100034, China E-Mail: lxm2128@ 123456163.com .
                Article
                CMJ-2019-1343
                10.1097/CM9.0000000000000542
                7028187
                31764175
                73414e3d-27df-4246-88fb-28ebdea6d7ab
                Copyright © 2019 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 13 August 2019
                Categories
                Review Articles
                Custom metadata
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                alternative splicing,cancer cell,hallmark,therapy,tumor microenvironment

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