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Relationship between microRNA genes incidence and cancer-associated genomic regions in canine tumors: a comprehensive bioinformatics study

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Abstract

The role of microRNAs (miRNAs) in human cancer biology has been confirmed on a genome-wide scale through the high incidence of these genes in cancer-associated regions. We analyzed the association between canine miRNA genes and cancer-associated regions (deleted and amplified regions) using previously published array of comparative genomic hybridization data on 268 canine cancer samples—comprising osteosarcoma, breast cancer, leukemia, and colorectal cancer. We also assessed this relationship apropos the incidence of miRNA genes in the CpG islands of the canine genome assembly. The association was evaluated using the mixed-effects Poisson regression analysis. Our analyses revealed that 135 miRNA genes were exactly located in the aberrated regions: 77 (57 %) in the loss and 58 (43 %) in amplified regions. Our findings indicated that the miRNA genes were located more frequently in the deleted regions as well as in the CpG islands than in all other regions. Additionally, with the exception of leukemia, the amplified regions significantly contained higher numbers of miRNA genes than did all the other regions.

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References

  • Akagi K, Suzuki T, Stephens RM, Jenkins NA, Copeland NG (2004) RTCGD: retroviral tagged cancer gene database. Nucleic Acids Res 32:D523–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albonico F, Mortarino M, Avallone G, Gioia G, Comazzi S, Roccabianca P (2013) The expression ratio of miR-17-5p and miR-155 correlates with grading in canine splenic lymphoma. Vet Immunol Immunopathol 155:117–123

    Article  CAS  PubMed  Google Scholar 

  • An O, Pendino V, D’Antonio M, Ratti E, Gentilini M, Ciccarelli FD (2014) NCG 4.0: the network of cancer genes in the era of massive mutational screenings of cancer genomes. Database (Oxford) 2014

  • Angstadt AY, Motsinger-Reif A, Thomas R, Kisseberth WC, Guillermo Couto C, Duval DL, Nielsen DM, Modiano JF, Breen M (2011) Characterization of canine osteosarcoma by array comparative genomic hybridization and RT-qPCR: signatures of genomic imbalance in canine osteosarcoma parallel the human counterpart. Genes Chromosom Cancer 50:859–874

    Article  CAS  PubMed  Google Scholar 

  • Boggs RM, Wright ZM, Stickney MJ, Porter WW, Murphy KE (2008) MicroRNA expression in canine mammary cancer. Mamm Genome 19:561–569

    Article  CAS  PubMed  Google Scholar 

  • Brueckner B, Stresemann C, Kuner R, Mund C, Musch T, Meister M, Sültmann H, Lyko F (2007) The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res 67:1419–1423

    Article  CAS  PubMed  Google Scholar 

  • Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI et al (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A 105:5166–5171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16:2733–2742

    Article  CAS  PubMed  Google Scholar 

  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102:13944–13949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Leva G, Calin GA, Croce CM (2006) MicroRNAs: fundamental facts and involvement in human diseases. Birth Defects Res C Embryo Today 78:180–189

    Article  PubMed  Google Scholar 

  • Durkin SG, Glover TW (2007) Chromosome fragile sites. Annu Rev Genet 41:169–192

    Article  CAS  PubMed  Google Scholar 

  • Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR (2004) A census of human cancer genes. Nat Rev Cancer 4:177–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hofacker IL (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31:3429–3431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huppi K, Volfovsky N, Mackiewicz M, Runfola T, Jones TL, Martin SE, Stephens R, Caplen NJ (2007) MicroRNAs and genomic instability. Semin Cancer Biol 17:65–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hutvágner G, Zamore PD (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056–2060

    Article  PubMed  Google Scholar 

  • Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6:590–610

    Article  CAS  PubMed  Google Scholar 

  • Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  CAS  PubMed  Google Scholar 

  • Jurka J, Kapitonov VV, Pavlicek A, Klonowski P, Kohany O, Walichiewicz J (2005) Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 110:462–467

    Article  CAS  PubMed  Google Scholar 

  • Karolchik D, Hinrichs AS, Furey TS, Roskin KM, Sugnet CW, Haussler D, Kent WJ (2004) The UCSC Table Browser data retrieval tool. Nucleic Acids Res 32:D493–D496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kloosterman WP, Plasterk RHA (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450

    Article  CAS  PubMed  Google Scholar 

  • Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laganà A, Russo F, Sismeiro C, Giugno R, Pulvirenti A, Ferro A (2010) Variability in the incidence of miRNAs and genes in fragile Sites and the role of repeats and CpG islands in the distribution of genetic material. PLoS ONE 5

  • Lee YS, Dutta A (2009) MicroRNAs in cancer. Annu Rev Pathol 4:199–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lingjaerde OC, Baumbusch LO, Liestøl K, Glad IK, Børresen-Dale A-L (2005) CGH-Explorer: a program for analysis of array-CGH data. Bioinformatics 21:821–822

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Xiong H, Ellis AE, Northrup NC, Rodriguez CO, O’Regan RM, Dalton S, Zhao S (2014) Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer. Cancer Res 74:5045–5056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ et al (2008) A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 105:13556–13561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McManus MT (2003) MicroRNAs and cancer. Semin Cancer Biol 13:253–258

    Article  CAS  PubMed  Google Scholar 

  • Mendell JT (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133:217–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, Shimotohno K (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25:2537–2545

    Article  CAS  PubMed  Google Scholar 

  • Nelson KM, Weiss GJ (2008) MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther 7:3655–3660

    Article  CAS  PubMed  Google Scholar 

  • Paczynska P, Grzemski A, Szydlowski M (2015) Distribution of miRNA genes in the pig genome. BMC Genet 16:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu C-G, Negrini M et al (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13:272–286

    Article  CAS  PubMed  Google Scholar 

  • Pillai RS, Bhattacharyya SN, Filipowicz W (2007) Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 17:118–126

    Article  CAS  PubMed  Google Scholar 

  • Roode SC, Rotroff D, Avery AC, Suter SE, Bienzle D, Schiffman JD, Motsinger-Reif A, Breen M (2015) Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation. Chromosome Res:1–28

  • Rossi S, Sevignani C, Nnadi SC, Siracusa LD, Calin GA (2008) Cancer-associated genomic regions (CAGRs) and noncoding RNAs: bioinformatics and therapeutic implications. Mamm Genome 19:526–540

    Article  CAS  PubMed  Google Scholar 

  • Scheinin I, Myllykangas S, Borze I, Böhling T, Knuutila S, Saharinen J (2008) CanGEM: mining gene copy number changes in cancer. Nucleic Acids Res 36:D830–D835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282:1479–1486

    Article  CAS  PubMed  Google Scholar 

  • Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, Demant P, Croce CM, Siracusa LD (2007) MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci U S A 104:8017–8022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh J, Nagaraju J (2008) In silico prediction and characterization of microRNAs from red flour beetle (Tribolium castaneum). Insect Mol Biol 17:427–436

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Zhou M, Mao Z-T, Hao D-P, Wang Z-Z, Li C-X (2013) Systematic analysis of genomic organization and structure of long non-coding RNAs in the human genome. FEBS Lett 587:976–982

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Le S, Sun L, Yan X, Zhang M, MacLeod J, LeRoy B, Northrup N, Ellis A, Yeatman TJ et al (2010) Copy number abnormalities in sporadic canine colorectal cancers. Genome Res 20:341–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uhl E, Krimer P, Schliekelman P, Tompkins SM, Suter S (2011) Identification of altered MicroRNA expression in canine lymphoid cell lines and cases of B- and T-Cell lymphomas. Genes Chromosomes Cancer 50:950–967

    Article  CAS  PubMed  Google Scholar 

  • Yoon S, Micheli GD (2005) Prediction of regulatory modules comprising microRNAs and target genes. Bioinformatics 21:ii93–ii100

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, Liang S, Naylor TL, Barchetti A, Ward MR et al (2006) microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A 103:9136–9141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9:133–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

I wish to thank Mr. Farshad Amouzadeh, who assisted in the proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, P.O. Box: 76169133, Kerman, Iran

    Mohamad Zamani-Ahmadmahmudi

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  1. Mohamad Zamani-Ahmadmahmudi
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Correspondence to Mohamad Zamani-Ahmadmahmudi.

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Electronic supplementary material

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Supplementary Table 1

MiRNA genes overlapped or matched with transposable elements (TEs) in canine genome assembly. Most of the miRNA genes simply overlapped with TEs. Additionally, 43 out of 54 suspected miRNAs were previously validated experimentally. Minimum-free energy was calculated for each miRNA. (DOCX 35 kb)

Supplementary Tables 2–8

Loss (green) and amplified (red) regions containing miRNA genes in various cancers. Start and end variables indicate the aberrated region position in the chromosome. (DOCX 43 kb)

Supplementary Table 9

Syntenic blocks of the canine regions containing miRNA genes located in loss regions in the human genome assembly. (DOCX 27 kb)

Supplementary Table 10

Syntenic blocks of the canine regions containing miRNA genes located in amplified regions in the human genome assembly. (DOCX 25 kb)

Supplementary Table 11

Syntenic blocks of the canine CpG islands with miRNA genes in human genome assembly. (DOCX 27 kb)

Supplementary Table 12

Exploration of human RefSeq genes that map to orthologous aberrant dog regions in CanGEM database. Most of the interested RefSeq genes indicated aberration changes in the human cancers (loss: green rows, gain: red rows, and CpG islands: yellow rows). (DOCX 31 kb)

Supplementary Table 13

Exploration of human RefSeq genes that map to orthologous aberrant dog regions in the Network of Cancer Genes (loss: green rows, gain: red rows, and CpG islands: yellow rows). (DOCX 25 kb)

Supplementary Table 14

CpG islands containing miRNA genes in the canine genome. Chr, start, end, and length denote chromosome location, start position, end position, and sequence length for each CpG island, respectively. (DOCX 28 kb)

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Zamani-Ahmadmahmudi, M. Relationship between microRNA genes incidence and cancer-associated genomic regions in canine tumors: a comprehensive bioinformatics study. Funct Integr Genomics 16, 143–152 (2016). https://doi.org/10.1007/s10142-016-0473-4

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  • DOI: https://doi.org/10.1007/s10142-016-0473-4

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