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Erschienen in:

2015 | Online First | Buchkapitel

Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease

verfasst von : Francesca Aguilo, Serena Di Cecilia, Martin J. Walsh

Erschienen in: Current Topics in Microbiology and Immunology

Verlag: Springer International Publishing

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Abstract

The long non-coding RNA CDKN2B-AS1, commonly referred to as the A ntisense N on-coding R NA in the I NK4 L ocus (ANRIL), is a 3.8-kb-long RNA transcribed from the short arm of human chromosome 9 on p21.3 that overlaps a critical region encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide association studies have identified this region with a remarkable and growing number of disease-associated DNA alterations and single nucleotide polymorphisms, which corresponds to increased susceptibility to human disease. Recent attention has been devoted on whether these alterations in the ANRIL sequence affect its expression levels and/or its splicing transcript variation, and in consequence, global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not only can regulate their immediate genomic neighbors in cis, but also has the capacity to regulate additional loci in trans. This action would further increase the complexity for mechanisms imposed through ANRIL and furthering the scope of this lncRNA in disease pathogenesis. In this chapter, we summarize the most recent findings on the investigation of ANRIL and provide a perspective on the biological and clinical significance of ANRIL as a putative biomarker, specifically, its potential role in directing cellular fates leading to cancer and cardiovascular disease.

de los Campos G, Gianola D, Allison DB (2010) Predicting genetic predisposition in humans: the promise of whole-genome markers. Nat Rev Genet 11(12):880–886

Gschwendtner A et al (2009) Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol 65(5):531–539CrossRefPubMedPubMedCentral

Matarin M et al (2008) Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21. Stroke 39(5):1586–1589CrossRefPubMedPubMedCentral

Helgadottir A et al (2008) The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet 40(2):217–224CrossRefPubMed

Zeggini E et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316(5829):1336–1341CrossRefPubMedPubMedCentral

Scott LJ et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316(5829):1341–1345CrossRefPubMedPubMedCentral

Shete S et al (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41(8):899–904CrossRefPubMedPubMedCentral

Wrensch M et al (2009) Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 41(8):905–908CrossRefPubMedPubMedCentral

Cunnington MS et al (2010) Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression. PLoS Genet 6(4):e1000899CrossRefPubMedPubMedCentral

Bishop DT et al (2009) Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 41(8):920–925CrossRefPubMedPubMedCentral

Gil J, Peters G (2006) Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol 7(9):667–677CrossRefPubMed

Popov N, Gil J (2010) Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health. Epigenetics 5(8):685–690CrossRefPubMedPubMedCentral

Nobori T et al (1996) Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers. Proc Natl Acad Sci U S A 93(12):6203–6208CrossRefPubMedPubMedCentral

Behrmann I et al (2003) Characterization of methylthioadenosin phosphorylase (MTAP) expression in malignant melanoma. Am J Pathol 163(2):683–690CrossRefPubMedPubMedCentral

Schmid M et al (1998) Homozygous deletions of methylthioadenosine phosphorylase (MTAP) are more frequent than p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancers (NSCLC). Oncogene 17(20):2669–2675CrossRefPubMed

Pasmant E et al (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67(8):3963–3969CrossRefPubMed

Yu W et al (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451(7175):202–206CrossRefPubMedPubMedCentral

Sato K et al (2010) ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1. Oncol Rep 24(3):701–707PubMed

Rodriguez C et al (2010) CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus. Biochem Biophys Res Commun 392(2):129–134CrossRefPubMed

Jarinova O et al (2009) Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol 29(10):1671–1677CrossRefPubMed

Burd CE et al (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6(12):e1001233CrossRefPubMedPubMedCentral

Schmid M et al (2000) A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer. Oncogene 19(50):5747–5754CrossRefPubMed

Folkersen L et al (2009a) Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. PLoS ONE 4(11):e7677CrossRefPubMedPubMedCentral

Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276(5688):565–570CrossRefPubMed

Levine SS et al (2002) The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol Cell Biol 22(17):6070–6078CrossRefPubMedPubMedCentral

Margueron R et al (2008) Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell 32(4):503–518CrossRefPubMedPubMedCentral

Shen X et al (2008) EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 32(4):491–502CrossRefPubMedPubMedCentral

Cao R, Tsukada Y, Zhang Y (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20(6):845–854CrossRefPubMed

Wang H et al (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431(7010):873–878CrossRefPubMed

Mak W et al (2002) Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells. Curr Biol 12(12):1016–1020CrossRefPubMed

Zhao J et al (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322(5902):750–756CrossRefPubMedPubMedCentral

Fitzpatrick GV, Soloway PD, Higgins MJ (2002) Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet 32(3):426–431CrossRefPubMed

Pandey RR et al (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32(2):232–246CrossRefPubMed

Rinn JL et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323CrossRefPubMedPubMedCentral

Kotake Y et al (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30(16):1956–1962CrossRefPubMedPubMedCentral

Yap KL et al (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38(5):662–674CrossRefPubMedPubMedCentral

Aguilo F, Zhou MM, Walsh MJ (2011) Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression. Cancer Res 71(16):5365–5369CrossRefPubMedPubMedCentral

Holdt LM et al (2013) Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet 9(7):e1003588CrossRefPubMedPubMedCentral

Folkersen L et al (2009b) Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. PLoS ONE 4(11):e7677CrossRefPubMedPubMedCentral

Holdt LM et al (2010) ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol 30(3):620–627CrossRefPubMed

Holdt LM, Teupser D (2012) Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol 32(2):196–206CrossRefPubMed

Liu Y et al (2009) INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS ONE 4(4):e5027CrossRefPubMedPubMedCentral

Guttman M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227CrossRefPubMedPubMedCentral

Congrains A et al (2012) Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis 220(2):449–455CrossRefPubMed

Bochenek G et al (2013) The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10. Hum Mol Genet 22(22):4516–4527CrossRefPubMed

Harismendy O et al (2011) 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response. Nature 470(7333):264–268CrossRefPubMedPubMedCentral

Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296(5573):1653–1655CrossRefPubMed

Helgadottir A et al (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316(5830):1491–1493CrossRefPubMed

Malumbres M, Ortega S, Barbacid M (2000) Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors. Biol Chem 381(9–10):827–838PubMed

Minamino T et al (2003) Ras induces vascular smooth muscle cell senescence and inflammation in human atherosclerosis. Circulation 108(18):2264–2269CrossRefPubMed

Lusis AJ (2000) Atherosclerosis. Nature 407(6801):233–241CrossRefPubMedPubMedCentral

Lander ES et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921CrossRefPubMed

Dewannieux M, Esnault C, Heidmann T (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat Genet 35(1):41–48CrossRefPubMed

Burns KH, Boeke JD (2012) Human transposon tectonics. Cell 149(4):740–752CrossRefPubMedPubMedCentral

Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159CrossRefPubMed

Iacobucci I et al (2011) A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia. Leuk Res 35(8):1052–1059CrossRefPubMed

Stacey SN et al (2009) New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 41(8):909–914CrossRefPubMedPubMedCentral

Turnbull C et al (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42(6):504–507CrossRefPubMedPubMedCentral

Pasmant E et al (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J 25(2):444–448CrossRefPubMed

Zhang EB et al (2014) Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget 5(8):2276–2292CrossRefPubMedPubMedCentral

Chen D et al (2014) ANRIL inhibits p15(INK4b) through the TGFbeta1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol 289(1–2):91–96PubMed

Wan G et al (2013) Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal 25(5):1086–1095CrossRefPubMedPubMedCentral

Titel: Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease
verfasst von: Francesca Aguilo
Serena Di Cecilia
Martin J. Walsh
Verlag: Springer International Publishing
DOI: https://doi.org/10.1007/82_2015_455

Springer Professional

Abstract

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