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      Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

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          Abstract

          Long non-coding RNAs (lncRNAs) are members of the non-protein coding RNA family longer than 200 nucleotides. They participate in the regulation of gene and protein expression influencing apoptosis, cell proliferation and immune responses, thereby playing a critical role in the development and progression of various cancers, including colorectal cancer (CRC). As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality, its screening and early detection are crucial, so the identification of disease-specific biomarkers is necessary. LncRNAs are promising candidates as they are involved in carcinogenesis, and certain lncRNAs ( e.g., CCAT1, CRNDE, CRCAL1-4) show altered expression in adenomas, making them potential early diagnostic markers. In addition to being useful as tissue-specific markers, analysis of circulating lncRNAs ( e.g., CCAT1, CCAT2, BLACAT1, CRNDE, NEAT1, UCA1) in peripheral blood offers the possibility to establish minimally invasive, liquid biopsy-based diagnostic tests. This review article aims to describe the origin, structure, and functions of lncRNAs and to discuss their contribution to CRC development. Moreover, our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.

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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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            Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution.

            Contrary to the well known diffraction limit, the fluorescence microscope is in principle capable of unlimited resolution. The necessary elements are spatially structured illumination light and a nonlinear dependence of the fluorescence emission rate on the illumination intensity. As an example of this concept, this article experimentally demonstrates saturated structured-illumination microscopy, a recently proposed method in which the nonlinearity arises from saturation of the excited state. This method can be used in a simple, wide-field (nonscanning) microscope, uses only a single, inexpensive laser, and requires no unusual photophysical properties of the fluorophore. The practical resolving power is determined by the signal-to-noise ratio, which in turn is limited by photobleaching. Experimental results show that a 2D point resolution of <50 nm is possible on sufficiently bright and photostable samples.
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              Gene regulation by the act of long non-coding RNA transcription

              Long non-protein-coding RNAs (lncRNAs) are proposed to be the largest transcript class in the mouse and human transcriptomes. Two important questions are whether all lncRNAs are functional and how they could exert a function. Several lncRNAs have been shown to function through their product, but this is not the only possible mode of action. In this review we focus on a role for the process of lncRNA transcription, independent of the lncRNA product, in regulating protein-coding-gene activity in cis. We discuss examples where lncRNA transcription leads to gene silencing or activation, and describe strategies to determine if the lncRNA product or its transcription causes the regulatory effect.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 September 2019
                14 September 2019
                : 25
                : 34
                : 5026-5048
                Affiliations
                Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary. udvardyne_galamb.orsolya@ 123456semmelweis-univ.hu
                2 nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
                Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
                2 nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
                2 nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
                Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
                Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
                2 nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
                Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
                Author notes

                Author contributions: All authors contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.

                Supported by the National Research, Development and Innovation Office, No. NVKP_16-1-2016-0004.

                Corresponding author: Orsolya Galamb, MSc, PhD, Research Fellow, Senior Scientist, 2 nd Department of Internal Medicine, Semmelweis University, Szentkirályi Str 46, Budapest H-1088, Hungary. udvardyne_galamb.orsolya@ 123456semmelweis-univ.hu

                Telephone: +36-1-2660926 Fax: +36-1-2660816

                Article
                jWJG.v25.i34.pg5026
                10.3748/wjg.v25.i34.5026
                6747286
                31558855
                8dc93138-5f13-49f6-84b6-a1049b58a701
                ©The Author(s) 2019. 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
                : 25 June 2019
                : 26 July 2019
                : 7 August 2019
                Categories
                Review

                long non-coding rna,colorectal cancer,colorectal adenoma,circulating long non-coding rnas,exosome,biomarker,diagnostic marker,prognostic marker

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