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      Is Open Access

      MicroRNAs and long non-coding RNAs: prospects in diagnostics and therapy of cancer

      review-article
      ,
      Radiology and Oncology
      Versita, Warsaw
      microRNAs, long non-coding RNAs, diagnosis, therapy, biomarker

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          Abstract

          Background

          Non-coding RNAs (ncRNAs) are key regulatory molecules in cellular processes, and are potential biomarkers in many diseases. Currently, microRNAs and long non-coding RNAs are being pursued as diagnostic and prognostic biomarkers, and as therapeutic tools in cancer, since their expression profiling is able to distinguish different cancer types and classify their sub-types.

          Conclusions

          There are numerous studies confirming involvement of ncRNAs in cancer initiation, development and progression, but have only been recently identified as new diagnostic and prognostic tools. This can be beneficial in future medical cancer treatment options, since ncRNAs are natural antisense interactors included in regulation of many genes connected to survival and proliferation. Research is directed in development of useful markers for diagnosis and prognosis in cancer and in developing new RNA-based cancer therapies, of which some are already in clinical trials.

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          Most cited references71

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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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            A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

            The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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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
                Radiol Oncol
                Radiol Oncol
                RADO
                Radiology and Oncology
                Versita, Warsaw
                1318-2099
                1581-3207
                December 2013
                08 October 2013
                : 47
                : 4
                : 311-318
                Affiliations
                Department of Molecular Genetics, Institute of Pathology, Medical Faculty, University of Ljubljana, Slovenia
                Author notes
                Correspondence to: Prof. Damjan Glavac, Ph.D., Department of Molecular Genetics, Institute of Pathology, Medical Faulty, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. E-mail: damjan.glavac@ 123456mf.uni-lj.si

                Disclosure: No potential conflicts of interest were disclosed.

                Article
                rado-47-04-311
                10.2478/raon-2013-0062
                3814275
                a05aa1ee-861b-44e1-ac92-6f1f65e8a4a9
                Copyright © by Association of Radiology & Oncology

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 15 June 2013
                : 20 August 2013
                Categories
                Review

                Oncology & Radiotherapy
                micrornas,long non-coding rnas,diagnosis,therapy,biomarker
                Oncology & Radiotherapy
                micrornas, long non-coding rnas, diagnosis, therapy, biomarker

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