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      Long Non-Coding RNA and Breast Cancer

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          Abstract

          Breast cancer, one of the most common diseases among women, is regarded as a heterogeneous and complicated disease that remains a major public health concern. Recently, owing to the development of next-generation sequencing technologies, long non-coding RNAs have received extensive attention. Numerous studies reveal that long non-coding RNAs are playing important roles in tumor development. Although the biological function and molecular mechanisms of long non-coding RNAs remain enigmatic, recent researchers have demonstrated that an array of long non-coding RNAs express abnormally in cancers, including breast cancer. Herein, we summarized the latest literature about long non-coding RNAs in breast cancer, with a particular focus on the multiple molecular roles of regulatory long non-coding RNAs that regulate cell proliferation, invasion, metastasis, and apoptosis.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            RNA maps reveal new RNA classes and a possible function for pervasive transcription.

            Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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              Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.

              Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Technol Cancer Res Treat
                Technol. Cancer Res. Treat
                TCT
                sptct
                Technology in Cancer Research & Treatment
                SAGE Publications (Sage CA: Los Angeles, CA )
                1533-0346
                1533-0338
                14 April 2019
                2019
                : 18
                : 1533033819843889
                Affiliations
                [1 ]Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [2 ]School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China
                [3 ]Cancer Research Institute of Wuhan, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [4 ]Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                Author notes
                [*]Zhongxin Lu, PhD, Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No 26, Shengli St, Jiangan District, Wuhan 430014, China. Email: lzx71@ 123456yahoo.com
                [*]Yong Ning, PhD, School of Laboratory Medicine, Hubei University of Chinese Medicine, No 1, Huangjia Lake West Road, Wuhan 430065, China. Email: ningyong128@ 123456163.com
                Author information
                https://orcid.org/0000-0002-3365-0881
                Article
                10.1177_1533033819843889
                10.1177/1533033819843889
                6466467
                30983509
                142c96c5-09d1-4962-91a2-1e05fe065ea6
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 14 September 2018
                : 7 January 2019
                : 21 March 2019
                Funding
                Funded by: Science and technology support program (foreign scientific and technological cooperation) of Hubei Province;
                Award ID: 2015BHE022
                Categories
                Review
                Custom metadata
                corrected-proof

                long non-coding rna,breast cancer,molecular mechanisms,cell proliferation,invasion,metastasis,apoptosis

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