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



      Radiology and Oncology

      Versita, Warsaw

      microRNAs, long non-coding RNAs, diagnosis, therapy, biomarker

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          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.


          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 references 70

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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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              miR-21-mediated tumor growth.

               Anna H. Wu,  L Si,  S Zhu (2007)
              MicroRNAs (miRNAs) are approximately 22 nucleotide non-coding RNA molecules that regulate gene expression post-transcriptionally. Although aberrant expression of miRNAs in various human cancers suggests a role for miRNAs in tumorigenesis, it remains largely unclear as to whether knockdown of a specific miRNA affects tumor growth. In this study, we profiled miRNA expression in matched normal breast tissue and breast tumor tissues by TaqMan real-time polymerase chain reaction miRNA array methods. Consistent with previous findings, we found that miR-21 was highly overexpressed in breast tumors compared to the matched normal breast tissues among 157 human miRNAs analysed. To better evaluate the role of miR-21 in tumorigenesis, we transfected breast cancer MCF-7 cells with anti-miR-21 oligonucleotides and found that anti-miR-21 suppressed both cell growth in vitro and tumor growth in the xenograft mouse model. Furthermore, this anti-miR-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic Bcl-2 in anti-miR-21-treated tumor cells. Together, these results suggest that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, it may serve as a novel therapeutic target.

                Author and article information

                Radiol Oncol
                Radiol Oncol
                Radiology and Oncology
                Versita, Warsaw
                December 2013
                08 October 2013
                : 47
                : 4
                : 311-318
                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.

                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/).


                Oncology & Radiotherapy

                micrornas, long non-coding rnas, diagnosis, therapy, biomarker


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