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      Dysregulated expression of long noncoding RNAs in gynecologic cancers

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          Abstract

          Cancers of the female reproductive system include ovarian, uterine, vaginal, cervical and vulvar cancers, which are termed gynecologic cancer. The emergence of long noncoding RNAs (lncRNAs), which are believed to play a crucial role in several different biological processes, has made the regulation of gene expression more complex. Although the function of lncRNAs is still rather elusive, their broad involvement in the initiation and progression of various cancers is clear. They are also involved in the pathogenesis of cancers of the female reproductive system. LncRNAs play a critical physiological role in apoptosis, metastasis, invasion, migration and cell proliferation in these cancers. Different expression profiles of lncRNAs have been observed in various types of tumors compared with normal tissues and between malignant and benign tumors. These differential expression patterns may lead to the promotion or suppression of cancer development and tumorigenesis. In the current review, we present the lncRNAs that show a differential expression between cancerous and normal tissues in ovarian, cervical and endometrial cancers, and highlight the associations between lncRNAs and some of the molecular pathways involved in these cancers.

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          Most cited references105

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          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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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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              Identification of mammalian microRNA host genes and transcription units.

              To derive a global perspective on the transcription of microRNAs (miRNAs) in mammals, we annotated the genomic position and context of this class of noncoding RNAs (ncRNAs) in the human and mouse genomes. Of the 232 known mammalian miRNAs, we found that 161 overlap with 123 defined transcription units (TUs). We identified miRNAs within introns of 90 protein-coding genes with a broad spectrum of molecular functions, and in both introns and exons of 66 mRNA-like noncoding RNAs (mlncRNAs). In addition, novel families of miRNAs based on host gene identity were identified. The transcription patterns of all miRNA host genes were curated from a variety of sources illustrating spatial, temporal, and physiological regulation of miRNA expression. These findings strongly suggest that miRNAs are transcribed in parallel with their host transcripts, and that the two different transcription classes of miRNAs ('exonic' and 'intronic') identified here may require slightly different mechanisms of biogenesis.
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                Author and article information

                Contributors
                MERYET-M@baclesse.unicancer.fr
                nikzad.kaums@gmail.com , hnikzad@yahoo.com
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                21 June 2017
                21 June 2017
                2017
                : 16
                : 107
                Affiliations
                [1 ]ISNI 0000 0004 0612 1049, GRID grid.444768.d, Gametogenesis Research Center, , Kashan University of Medical Science, ; Kashan, Iran
                [2 ]ISNI 0000 0001 2186 4076, GRID grid.412043.0, , Normandie Univ, UNICAEN, INSERM, ANTICIPE U1086 (Interdisciplinary Research for Cancers prevention and treatment, axis BioTICLA (Biology and Innovative Therapeutics for Ovarian Cancer), ; Caen, France
                [3 ]ISNI 0000 0001 1781 3962, GRID grid.412266.5, Department of Nanobiotechnology, Faculty of Biological Sciences, , Tarbiat Modares University, ; Tehran, Iran
                [4 ]ISNI 0000 0004 0612 1049, GRID grid.444768.d, Anatomical Sciences Research Center, , Kashan University of Medical Sciences, ; Kashan, Iran
                [5 ]Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan, Iran
                [6 ]ISNI 0000 0001 2175 1768, GRID grid.418189.d, , UNICANCER, Comprehensive Cancer Centre François Baclesse, ; Caen, France
                Article
                671
                10.1186/s12943-017-0671-2
                5480155
                28637507
                b3fa9ad2-781c-4db5-8483-1aa835493828
                © The Author(s). 2017

                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
                : 6 March 2017
                : 26 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003968, Iran National Science Foundation;
                Award ID: 95819873
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Oncology & Radiotherapy
                long noncoding rna,female reproductive system,ovarian cancer,endometrial cancer,cervical cancer

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