“Going Long”: Long Non-Coding RNAs as Biomarkers
2014; Lippincott Williams & Wilkins; Volume: 115; Issue: 7 Linguagem: Tagalog
10.1161/circresaha.114.304839
ISSN1524-4571
AutoresPhilipp Skroblin, Manuel Mayr,
Tópico(s)RNA Research and Splicing
ResumoHomeCirculation ResearchVol. 115, No. 7"Going Long": Long Non-Coding RNAs as Biomarkers Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUB"Going Long": Long Non-Coding RNAs as Biomarkers Philipp Skroblin and Manuel Mayr Philipp SkroblinPhilipp Skroblin From the Cardiovascular Division, King's British Heart Foundation Centre, King's College London, London, United Kingdom. and Manuel MayrManuel Mayr From the Cardiovascular Division, King's British Heart Foundation Centre, King's College London, London, United Kingdom. Originally published12 Sep 2014https://doi.org/10.1161/CIRCRESAHA.114.304839Circulation Research. 2014;115:607–609Protein-coding sequences constitute <2% of the human genome. The majority of the remaining 98% was long assumed to be nonfunctional junk DNA but there is increasing evidence that ≤85% of the human genome is transcribed into RNA.1 Noncoding sequences in the genome increase proportionally with the complexity of the organism, implying a need for additional transcriptional regulation in the evolution of eukaryotic organisms. Thus, the vast majority of the human transcriptome is noncoding RNA, which is divided into short noncoding RNAs ( 200 nucleotides). Since their discovery in 2001, miRNAs have been studied extensively and fundamental insights have been obtained about their synthesis, their repression of target genes, and their involvement in disease processes. Indeed, miRNA therapeutics are already tested in clinical trials.Article, see p 668After the explosion of interest in miRNAs, the attention is now shifting to lncRNAs. lncRNAs have emerged as another important layer of gene regulation. On the basis of their genomic loci, lncRNAs can be classified into 5 categories (Figure): (1) sense lncRNAs are transcribed from a locus overlapping with a protein-coding gene; (2) antisense lncRNAs loci overlap with the antisense strand of protein-coding gene; (3) bidirectional lncRNAs are located on the antisense strand of a protein-coding gene whose start codon is 20 linear and several circular isoforms of ANRIL have been identified.16 The risk genotype of the lead single-nucleotide polymorphism for coronary artery disease located in the ANRIL locus (rs10757278-G) causes an increased expression of some ANRIL variants but a decrease in others.16 Similarly, MALAT1 has 11 variants and MIAT has 4. Assessing the levels of particular variants might provide key information, which is missed when the analytic tools do not distinguish between variants. A more detailed analysis as to which splice variants of lncRNAs are differentially expressed in patients with MI will be required. Other drawbacks of the study are the lack of an independent validation cohort and confounding by inflammatory responses associated with MI. Although KCNQ1OT1 and MIAT did not show significant associations with inflammatory markers, antisense hypoxia inducible factor 1α was positively correlated with inflammation. All selected lncRNAs have been identified in noncardiac tissues. This lack of cardiac specificity questions their usefulness as predictors of cardiac dysfunction. At best, measuring lncRNA expression in full blood might reflect inflammation at the site of MI.lncRNA research is still in its infancy and a better characterization of the lncRNA transcriptome, advances in the understanding of lncRNA function and improved analytic tools will allow to replicate and extend the findings presented by such early studies.13 Because of the high number of different lncRNAs, next-generation sequencing methods will be instrumental in exploring lncRNAs in health and disease. Whether lncRNAs are better predictive biomarkers than existing cardiovascular biomarkers or other noncoding RNAs, such as miRNAs,17 awaits confirmation in future studies.Sources of FundingM. Mayr is a Senior Fellow of the British Heart Foundation and member of a network on MicroRNA-based Therapeutic Strategies in Vascular Disease funded by the Foundation Leducq. The research was funded/supported by the National Institute of Health Research Biomedical Research Centre based at Guy's and St Thomas' National Health Service Foundation Trust and King's College London in partnership with King's College Hospital.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart AssociationCorrespondence to Manuel Mayr, MD, PhD, King's British Heart Foundation Centre, King's College London, 125 Coldharbour Ln, London SE5 9NU, United Kingdom. E-mail [email protected]References1. Hangauer MJ, Vaughn IW, McManus MT. Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs.PLoS Genet. 2013; 9:e1003569.CrossrefMedlineGoogle Scholar2. Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation.Nat Struct Mol Biol. 2013; 20:300–307.CrossrefMedlineGoogle Scholar3. Xie C, Yuan J, Li H, Li M, Zhao G, Bu D, Zhu W, Wu W, Chen R, Zhao Y. NONCODEv4: exploring the world of long non-coding RNA genes.Nucleic Acids Res. 2014; 42:D98–103.CrossrefMedlineGoogle Scholar4. Klattenhoff CA, Scheuermann JC, Surface LE, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.Cell. 2013; 152:570–583.CrossrefMedlineGoogle Scholar5. He S, Gu W, Li Y, Zhu H. ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians.BMC Evol Biol. 2013; 13:247.CrossrefMedlineGoogle Scholar6. Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA.Arterioscler Thromb Vasc Biol. 2014; 34:1249–1259.LinkGoogle Scholar7. Wang K, Liu F, Zhou LY, Long B, Yuan SM, Wang Y, Liu CY, Sun T, Zhang XJ, Li PF. The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.Circ Res. 2014; 114:1377–1388.LinkGoogle Scholar8. Wang K, Long B, Zhou LY, Liu F, Zhou QY, Liu CY, Fan YY, Li PF. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation.Nat Commun. 2014; 5:3596.CrossrefMedlineGoogle Scholar9. Zangrando J, Zhang L, Vausort M, Maskali F, Marie PY, Wagner DR, Devaux Y. Identification of candidate long non-coding RNAs in response to myocardial infarction.BMC Genomics. 2014; 15:460.CrossrefMedlineGoogle Scholar10. Ounzain S, Micheletti R, Beckmann T, et al. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs [published online ahead of print Apr 30, 2014].Eur Heart J. doi: 10.1093/eurheartj/ehu180.Google Scholar11. Yang KC, Yamada KA, Patel AY, Topkara VK, George I, Cheema FH, Ewald GA, Mann DL, Nerbonne JM. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.Circulation. 2014; 129:1009–1021.LinkGoogle Scholar12. Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, Lemesle G, de Groote P, Pinet F, Thum T. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure.Circ Res. 2014; 114:1569–1575.LinkGoogle Scholar13. Vausort M, Wagner DR, Devaux Y. Long noncoding RNAs in patients with acute myocardial infarction.Circ Res. 2014; 115:668–677.LinkGoogle Scholar14. Michalik KM, You X, Manavski Y, Doddaballapur A, Zörnig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth.Circ Res. 2014; 114:1389–1397.LinkGoogle Scholar15. Meder B, Rühle F, Weis T, et al. A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.Eur Heart J. 2014; 35:1069–1077.CrossrefMedlineGoogle Scholar16. Congrains A, Kamide K, Ohishi M, Rakugi H. ANRIL: Molecular mechanisms and implications in human health.Int J Mol Sci. 2013; 14:1278–1292.CrossrefMedlineGoogle Scholar17. Zampetaki A, Willeit P, Tilling L, et al. Prospective study on circulating microRNAs and risk of myocardial infarction.J Am Coll Cardiol. 2012; 60:290–299.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Marinescu M, Lazar A, Marta M, Cozma A and Catana C (2022) Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia–Reperfusion Injury, International Journal of Molecular Sciences, 10.3390/ijms23052728, 23:5, (2728) Razeghian-Jahromi I, Karimi Akhormeh A, Zibaeenezhad M and Borghini A (2022) The Role of ANRIL in Atherosclerosis, Disease Markers, 10.1155/2022/8859677, 2022, (1-10), Online publication date: 9-Feb-2022. Hosen M, Li Q, Liu Y, Zietzer A, Maus K, Goody P, Uchida S, Latz E, Werner N, Nickenig G and Jansen F (2021) CAD increases the long noncoding RNA PUNISHER in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling, Molecular Therapy - Nucleic Acids, 10.1016/j.omtn.2021.05.023, 25, (388-405), Online publication date: 1-Sep-2021. Zong Z, Hu C, Zhou T, Yu Z, Tang F, Tian H, Li H and Wang H (2021) Nine-long non-coding ribonucleic acid signature can improve the survival prediction of colorectal cancer, World Journal of Gastrointestinal Surgery, 10.4240/wjgs.v13.i2.210, 13:2, (210-221), Online publication date: 27-Feb-2021. Zong Z, Li H, Yu Z, Tang F, Zhu X, Tian H, Zhou T and Wang H (2020) Prognostic thirteen-long non-coding RNAs (IncRNAs) could improve the survival prediction of gastric cancer, Gastroenterología y Hepatología, 10.1016/j.gastrohep.2020.01.016, 43:10, (598-606), Online publication date: 1-Dec-2020. Zong Z, Li H, Yu Z, Tang F, Zhu X, Tian H, Zhou T and Wang H (2020) Prognostic thirteen-long non-coding RNAs (IncRNAs) could improve the survival prediction of gastric cancer, Gastroenterología y Hepatología (English Edition), 10.1016/j.gastre.2020.01.019, 43:10, (598-606), Online publication date: 1-Dec-2020. Wu N, Li J, Chen X, Xiang Y, Wu L, Li C, Zhang H, Tong S, Zhong L and Li Y (2020) Identification of Long Non-Coding RNA and Circular RNA Expression Profiles in Atrial Fibrillation, Heart, Lung and Circulation, 10.1016/j.hlc.2019.10.018, 29:7, (e157-e167), Online publication date: 1-Jul-2020. Chen L, Qu H, Guo M, Zhang Y, Cui Y, Yang Q, Bai R and Shi D (2019) ANRIL and atherosclerosis, Journal of Clinical Pharmacy and Therapeutics, 10.1111/jcpt.13060, 45:2, (240-248), Online publication date: 1-Apr-2020. Zhu B, Cheng X, Jiang Y, Cheng M, Chen L, Bao J and Tang X (2020) Silencing of KCNQ1OT1 Decreases Oxidative Stress and Pyroptosis of Renal Tubular Epithelial Cells, Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 10.2147/DMSO.S225791, Volume 13, (365-375) Li Y, Yan G, Zhang J, Chen W, Ding T, Yin Y, Li M, Zhu Y, Sun S, Yuan J and Guo Z (2019) LncRNA HOXA11‐AS regulates calcium oxalate crystal–induced renal inflammation via miR‐124‐3p/MCP‐1, Journal of Cellular and Molecular Medicine, 10.1111/jcmm.14706, 24:1, (238-249), Online publication date: 1-Jan-2020. Chen C, Tang Y, Sun H, Lin X and Jiang B (2019) The roles of long noncoding RNAs in myocardial pathophysiology, Bioscience Reports, 10.1042/BSR20190966, 39:11, Online publication date: 29-Nov-2019. Wu C, Song H, Wang Y, Gao L, Cai Y, Cheng Q, Chen Y, Zheng Z, Liao Y, Lin J, Xie B, Cai W, Li S, Liao L and Yan X (2019) Long non-coding RNA TCONS_00000200 as a non-invasive biomarker in patients with intracranial aneurysm, Bioscience Reports, 10.1042/BSR20182224, 39:11, Online publication date: 29-Nov-2019. Sarfi M, Abbastabar M and Khalili E (2019) Long noncoding RNAs biomarker‐based cancer assessment, Journal of Cellular Physiology, 10.1002/jcp.28417, 234:10, (16971-16986), Online publication date: 1-Oct-2019. Moreau P, Örd T, Downes N, Niskanen H, Bouvy-Liivrand M, Aavik E, Ylä-Herttuala S and Kaikkonen M (2018) Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2018.00159, 5 Poller W, Dimmeler S, Heymans S, Zeller T, Haas J, Karakas M, Leistner D, Jakob P, Nakagawa S, Blankenberg S, Engelhardt S, Thum T, Weber C, Meder B, Hajjar R and Landmesser U (2017) Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives, European Heart Journal, 10.1093/eurheartj/ehx165, 39:29, (2704-2716), Online publication date: 1-Aug-2018. Sun S, Tang P, Feng M, Xiao J, Huang X, Li P, Ma R and Lan H (2017) Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b , Diabetes, 10.2337/db17-0816, 67:4, (731-744), Online publication date: 1-Apr-2018. Walter W, Alonso-Herranz L, Trappetti V, Crespo I, Ibberson M, Cedenilla M, Karaszewska A, Núñez V, Xenarios I, Arroyo A, Sánchez-Cabo F and Ricote M (2018) Deciphering the Dynamic Transcriptional and Post-transcriptional Networks of Macrophages in the Healthy Heart and after Myocardial Injury, Cell Reports, 10.1016/j.celrep.2018.03.029, 23:2, (622-636), Online publication date: 1-Apr-2018. Di Mauro V, Barandalla-Sobrados M and Catalucci D (2018) The noncoding-RNA landscape in cardiovascular health and disease, Non-coding RNA Research, 10.1016/j.ncrna.2018.02.001, 3:1, (12-19), Online publication date: 1-Mar-2018. Blankenberg S and Zeller T (2018) Standard and Novel Biomarkers Chronic Coronary Artery Disease, 10.1016/B978-0-323-42880-4.00009-1, (98-113), . Börnigen D and Zeller T (2018) Transcriptomics in Cardiovascular Medicine Encyclopedia of Cardiovascular Research and Medicine, 10.1016/B978-0-12-809657-4.99572-3, (558-571), . Zeller T (2018) OBSOLETE: Transciptomics in Cardiovascular Medicine Reference Module in Biomedical Sciences, 10.1016/B978-0-12-801238-3.99572-2, . Zampetaki A and Mayr M (2017) Long Noncoding RNAs and Angiogenesis, Circulation, 136:1, (80-82), Online publication date: 4-Jul-2017. Kiang K, Zhang X, Zhang G, Li N, Cheng S, Poon M, Pu J, Lui W and Leung G (2017) CRNDE Expression Positively Correlates with EGFR Activation and Modulates Glioma Cell Growth, Targeted Oncology, 10.1007/s11523-017-0488-3, 12:3, (353-363), Online publication date: 1-Jun-2017. Sunderland N, Skroblin P, Barwari T, Huntley R, Lu R, Joshi A, Lovering R and Mayr M (2017) MicroRNA Biomarkers and Platelet Reactivity, Circulation Research, 120:2, (418-435), Online publication date: 20-Jan-2017. Zhao J, Song X and Wang K (2016) lncScore: alignment-free identification of long noncoding RNA from assembled novel transcripts, Scientific Reports, 10.1038/srep34838, 6:1, Online publication date: 1-Dec-2016. Bär C, Chatterjee S and Thum T (2016) Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy, Circulation, 134:19, (1484-1499), Online publication date: 8-Nov-2016. Xie W, Yuan S, Sun Z and Li Y (2016) Long noncoding and circular RNAs in lung cancer: advances and perspectives, Epigenomics, 10.2217/epi-2016-0036, 8:9, (1275-1287), Online publication date: 1-Sep-2016. Man H, Yan M, Lee J and Marsden P (2016) Epigenetic determinants of cardiovascular gene expression: vascular endothelium, Epigenomics, 10.2217/epi-2016-0012, 8:7, (959-979), Online publication date: 1-Jul-2016. Bakhtiarizadeh M, Hosseinpour B, Arefnezhad B, Shamabadi N, Salami S and Bureau T (2016) In silico prediction of long intergenic non-coding RNAs in sheep, Genome, 10.1139/gen-2015-0141, 59:4, (263-275), Online publication date: 1-Apr-2016. Liao J, He Q, Li M, Chen Y, Liu Y and Wang J (2016) LncRNA MIAT: Myocardial infarction associated and more, Gene, 10.1016/j.gene.2015.12.032, 578:2, (158-161), Online publication date: 1-Mar-2016. Duggirala A, Delogu F, Angelini T, Smith T, Caputo M, Rajakaruna C and Emanueli C (2015) Non coding RNAs in aortic aneurysmal disease, Frontiers in Genetics, 10.3389/fgene.2015.00125, 6 September 12, 2014Vol 115, Issue 7 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.114.304839PMID: 25214572 Originally publishedSeptember 12, 2014 KeywordsEditorialsRNA, untranslatedbiomarkersPDF download Advertisement SubjectsDiagnostic TestingGene Expression and RegulationHeart FailureOmics
Referência(s)