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      The non-coding RNAs of the H19-IGF2 imprinted loci: A focus on biological roles and therapeutic potential in Lung Cancer

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          Abstract

          Since it was first described, the imprinted cluster 11p15.5 has been reported to be deregulated in a variety of pediatric and adult cancers including that of the lung. Both protein coding and non-coding genes functioning as oncogenes or as tumor suppressor genes reside within this cluster. Oncomirs that can function as oncogenes or as tumor suppressors have also been reported. While a complete account of the role played by the 11p15.5 imprinted cluster in lung cancer is beyond the scope of this review, we will focus on the role of the non-coding RNAs processed from the H19-IGF2 loci. A special emphasis will be given to the H19/miR-675 gene locus. Their potential diagnostic and therapeutic use in lung cancer will be described.

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          MicroRNA biogenesis: coordinated cropping and dicing.

          V Kim (2005)
          The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
          Article 0 comments Cited 711 times – based on 0 reviews     Review now
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            Identification of mammalian microRNA host genes and transcription units.

            Antony Rodriguez, Sam Griffiths-Jones, Jennifer Ashurst … (2004)
            To derive a global perspective on the transcription of microRNAs (miRNAs) in mammals, we annotated the genomic position and context of this class of noncoding RNAs (ncRNAs) in the human and mouse genomes. Of the 232 known mammalian miRNAs, we found that 161 overlap with 123 defined transcription units (TUs). We identified miRNAs within introns of 90 protein-coding genes with a broad spectrum of molecular functions, and in both introns and exons of 66 mRNA-like noncoding RNAs (mlncRNAs). In addition, novel families of miRNAs based on host gene identity were identified. The transcription patterns of all miRNA host genes were curated from a variety of sources illustrating spatial, temporal, and physiological regulation of miRNA expression. These findings strongly suggest that miRNAs are transcribed in parallel with their host transcripts, and that the two different transcription classes of miRNAs ('exonic' and 'intronic') identified here may require slightly different mechanisms of biogenesis.
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              Exosomal microRNA: a diagnostic marker for lung cancer.

              Guilherme Rabinowits, Cicek Gercel-Taylor, Jamie Day … (2009)
              To date, there is no screening test for lung cancer shown to affect overall mortality. MicroRNAs (miRNAs) are a class of small noncoding RNA genes found to be abnormally expressed in several types of cancer, suggesting a role in the pathogenesis of human cancer. We evaluated the circulating levels of tumor exosomes, exosomal small RNA, and specific exosomal miRNAs in patients with and without lung adenocarcinoma, correlating the levels with the American Joint Committee on Cancer (AJCC) disease stage to validate it as an acceptable marker for diagnosis and prognosis in patients with adenocarcinoma of the lung. To date, 27 patients with lung adenocarcinoma AJCC stages I-IV and 9 controls, all aged 21-80 years, were enrolled in the study. Small RNA was detected in the circulating exosomes. The mean exosome concentration was 2.85 mg/mL (95% CI, 1.94-3.76) for the lung adenocarcinoma group versus 0.77 mg/mL (95% CI, 0.68-0.86) for the control group (P < .001). The mean miRNA concentration was 158.6 ng/mL (95% CI, 145.7-171.5) for the lung adenocarcinoma group versus 68.1 ng/mL (95% CI, 57.2-78.9) for the control group (P < .001). Comparisons between peripheral circulation miRNA-derived exosomes and miRNA-derived tumors indicated that the miRNA signatures were not significantly different. The significant difference in total exosome and miRNA levels between lung cancer patients and controls, and the similarity between the circulating exosomal miRNA and the tumor-derived miRNA patterns, suggest that circulating exosomal miRNA might be useful as a screening test for lung adenocarcinoma. No correlation between the exosomal miRNA levels and the stage of disease can be made at this point.
              Article 0 comments Cited 469 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Imad J Matouk: imad.matouq@mail.huji.ac.il
                David Halle: halledavid57@gmail.com
                Michal Gilon: michal.gilon@biocancell.com
                Abraham Hochberg: avraham.hochberg@biocancell.com
                Journal
                Journal ID (nlm-ta): J Transl Med
                Journal ID (iso-abbrev): J Transl Med
                Title: Journal of Translational Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1479-5876
                Publication date (Electronic): 9 April 2015
                Publication date PMC-release: 9 April 2015
                Publication date Collection: 2015
                Volume: 13
                Electronic Location Identifier: 113
                Affiliations
                Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904 Israel
                Article
                Publisher ID: 467
                DOI: 10.1186/s12967-015-0467-3
                PMC ID: 4397711
                PubMed ID: 25884481
                SO-VID: 83ab1eeb-8499-48fa-895d-f6a0f72f4c21
                Copyright © © Matouk et al.; licensee BioMed Central. 2015
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
                Date received : 30 November 2014
                Date accepted : 18 March 2015
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Medicine
                Keywords: h19,mir-675,igf2,oncomirs,lung cancer,imprinted cluster
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: h19, mir-675, igf2, oncomirs, lung cancer, imprinted cluster

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