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      Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

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          Abstract

          Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.

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          Most cited references142

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          Epigenetics in cancer.

          Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
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            MicroRNA biogenesis: coordinated cropping and dicing.

            V Kim (2005)
            The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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              Epigenetic gene silencing in cancer: the DNA hypermethylome.

              Epigenetic gene inactivation in transformed cells involves many 'belts of silencing'. One of the best-known lesions of the malignant cell is the transcriptional repression of tumor-suppressor genes by promoter CpG island hypermethylation. We are in the process of completing the molecular dissection of the entire epigenetic machinery involved in methylation-associated silencing, such as DNA methyltransferases, methyl-CpG binding domain proteins, histone deacetylases, histone methyltransferases, histone demethylases and Polycomb proteins. The first indications are also starting to emerge about how the combination of cellular selection and targeted pathways leads to abnormal DNA methylation. One thing is certain already, promoter CpG island hypermethylation of tumor-suppressor genes is a common hallmark of all human cancers. It affects all cellular pathways with a tumor-type specific profile, and in addition to classical tumor-suppressor and DNA repair genes, it includes genes involved in premature aging and microRNAs with growth inhibitory functions. The importance of hypermethylation events is already in evidence at the bedside of cancer patients in the form of cancer detection markers and chemotherapy predictors, and in the approval of epigenetic drugs for the treatment of hematological malignancies. In the very near future, the synergy of candidate gene approaches and large-scale epigenomic technologies, such as methyl-DIP, will yield the complete DNA hypermethylome of cancer cells.
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                Author and article information

                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                21 September 2016
                21 September 2016
                : 22
                : 35
                : 7951-7962
                Affiliations
                Kelly Cristina da Silva Oliveira, Taíssa Maíra Thomaz Araújo, Camila Inagaki Albuquerque, Gabriela Alcantara Barata, Fernando Augusto Rodrigues Mello Junior, André Salim Khayat, Paulo Pimentel de Assumpção, Danielle Queiroz Calcagno, Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Hospital Universitário João de Barros Barreto, Belém, PA 66073-000, Brazil
                Carolina Oliveira Gigek, Mariana Ferreira Leal, Fernanda Wisnieski, Marília Cardoso Smith, Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo 04021-001, Brazil
                Rommel Mário Rodriguez Burbano, Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA 66073-000, Brazil
                Author notes

                Author contributions: da Silva Oliveira KC and Calcagno DQ performed the review design; da Silva Oliveira KC, Thomaz Araújo TM, Albuquerque CI and Calcagno DQ collected the data; Thomaz Araújo TM, Albuquerque CI, Barata GA, Rodrigues Mello Junior FA and Calcagno DQ wrote the paper; Gigek CO performed corrections and suggestions; de Assumpção PP, Rodriguez Burbano RM and Smith MC revised the paper critically; all the authors contributed to this manuscript.

                Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo; the Conselho Nacional de Desenvolvimento Científico e Tecnológico; and the Coordenação de Aperfeiçooamento de Pessoal de Nível Superior .

                Correspondence to: Danielle Queiroz Calcagno, PhD, Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Hospital Universitário João de Barros Barreto, 2º Piso da UNACON, Av. Mundurucus, Belém, PA 66073-000, Brazil. danicalcagno@ 123456gmail.com

                Telephone: +55-91-32016776

                Article
                jWJG.v22.i35.pg7951
                10.3748/wjg.v22.i35.7951
                5028809
                27672290
                a5e5c4f1-d8df-4ee7-a91f-40683274d345
                ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 12 March 2016
                : 14 June 2016
                : 1 August 2016
                Categories
                Review

                gastric cancer,epigenetic,diagnostic biomarkers,mirnas,prognostic biomarkers

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