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      Long noncoding RNAs in cancer: mechanisms of action and technological advancements

      review-article
      , ,
      Molecular Cancer
      BioMed Central

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          Abstract

          The previous decade has seen long non-coding RNAs (lncRNAs) rise from obscurity to being defined as a category of genetic elements, leaving its mark on the field of cancer biology. With the current number of curated lncRNAs increasing by 10,000 in the last five years, the field is moving from annotation of lncRNA expression in various tumours to understanding their importance in the key cancer signalling networks and characteristic behaviours. Here, we summarize the previously identified as well as recently discovered mechanisms of lncRNA function and their roles in the hallmarks of cancer. Furthermore, we identify novel technologies for investigation of lncRNA properties and their function in carcinogenesis, which will be important for their translation to the clinic as novel biomarkers and therapeutic targets.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12943-016-0530-6) contains supplementary material, which is available to authorized users.

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          Most cited references78

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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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              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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                Author and article information

                Contributors
                m.dinger@garvan.org.au
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                27 May 2016
                27 May 2016
                2016
                : 15
                : 43
                Affiliations
                [ ]Genome Informatics, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW Australia
                [ ]Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, Sydney, NSW Australia
                Article
                530
                10.1186/s12943-016-0530-6
                4884374
                27233618
                c10d7e70-db12-4eb2-9f43-6e51e47245c5
                © Bartonicek et al. 2016

                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
                : 24 February 2016
                : 12 May 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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