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  • Oncogenomics
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Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer

Oncogene volume 23, pages 6684–6692 (2004)Cite this article

Abstract

A large fraction of transcripts are expressed antisense to introns of known genes in the human genome. Here we show the construction and use of a cDNA microarray platform enriched in intronic transcripts to assess their biological relevance in pathological conditions. To validate the approach, prostate cancer was used as a model, and 27 patient tumor samples with Gleason scores ranging from 5 to 10 were analyzed. We find that a considerably higher fraction (6.6%, [23/346]) of intronic transcripts are significantly correlated (P⩽0.001) to the degree of prostate tumor differentiation (Gleason score) when compared to transcripts from unannotated genomic regions (1%, [6/539]) or from exons of known genes (2%, [27/1369]). Among the top twelve transcripts most correlated to tumor differentiation, six are antisense intronic messages as shown by orientation-specific RT-PCR or Northern blot analysis with strand-specific riboprobe. Orientation-specific real-time RT–PCR with six tumor samples, confirmed the correlation (P=0.024) between the low/high degrees of tumor differentiation and antisense intronic RASSF1 transcript levels. The need to use intron arrays to reveal the transcriptome profile of antisense intronic RNA in cancer has clearly emerged.

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Abbreviations

GS:

Gleason score

References

  • Best CJ, Leiva IM, Chuaqui RF, Gillespie JW, Duray PH, Murgai M, Zhao Y, Simon R, Kang JJ, Green JE, Bostwick DG, Linehan WM and Emmert-Buck MR . (2003). Diagn. Mol. Pathol., 12, 63–70.

  • Brentani H, Caballero OL, Camargo AA, Da Silva AM, Da Silva Jr WA, Neto ED, Grivet M, Gruber A, Guimaraes PE, Hide W, Iseli C, Jongeneel CV, Kelso J, Nagai MA, Ojopi EP, Osorio EC, Reis EM, Riggins GJ, Simpson AJ, De Souza S, Stevenson BJ, Strausberg RL, Tajara EH and Verjovski-Almeida S . (2003). Proc. Natl. Acad. Sci. USA, 100, 13418–13423.

  • Brunschwig EB, Wilson K, Mack D, Dawson D, Lawrence E, Willson JK, Lu S, Nosrati A, Rerko RM, Swinler S, Beard L, Lutterbaugh JD, Willis J, Platzer P and Markowitz S . (2003). Cancer Res., 63, 1568–1575.

  • Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM . (2004). Proc. Natl. Acad. Sci. USA, 101, 2999–3004.

  • Camargo AA, Samaia HP, Dias-Neto E, Simao DF, Migotto IA, Briones MR, Costa FF, Nagai MA, Verjovski-Almeida S, Zago MA, Andrade LE, Carrer H, El-Dorry HF, Espreafico EM, Habr-Gama A, Giannella-Neto D, Goldman GH, Gruber A, Hackel C, Kimura ET, Maciel RM, Marie SK, Martins EA, Nobrega MP, Paco-Larson ML, Pardini MI, Pereira GG, Pesquero JB, Rodrigues V, Rogatto SR, da Silva ID, Sogayar MC, Sonati MF, Tajara EH, Valentini SR, Alberto FL, Amaral ME, Aneas I, Arnaldi LA, de Assis AM, Bengtson MH, Bergamo NA, Bombonato V, de Camargo ME, Canevari RA, Carraro DM, Cerutti JM, Correa ML, Correa RF, Costa MC, Curcio C, Hokama PO, Ferreira AJ, Furuzawa GK, Gushiken T, Ho PL, Kimura E, Krieger JE, Leite LC, Majumder P, Marins M, Marques ER, Melo AS, Melo M, Mestriner CA, Miracca EC, Miranda DC, Nascimento AL, Nobrega FG, Ojopi EP, Pandolfi JR, Pessoa LG, Prevedel AC, Rahal P, Rainho CA, Reis EM, Ribeiro ML, da Ros N, da Sa RG, Slaes MM, Santa'anna SC, dos Santos ML, da Silva AM, da Silva NP, Silva Jr WA, da Silveira RA, Sousa JF, Stecconi D, Tsukumo F, Valente V, Soares F, Moreira ES, Nunes DN, Correa RG, Zalcberg H, Carvalho AF, Reis LF, Brentani RR, Simpson AJ and de Souza SJ . (2001). Proc. Natl. Acad. Sci. USA, 98, 12103–12108.

  • Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K and Gingeras TR . (2004). Cell, 116, 499–509.

  • Chen G and Courey AJ . (2000). Gene, 249, 1–16.

  • Dias-Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva Jr W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ and Simpson AJ . (2000). Proc. Natl. Acad. Sci. USA, 97, 3491–3496.

  • Epstein JI, Partin AW, Sauvageot J and Walsh PC . (1996). Am. J. Surg. Pathol., 20, 286–292.

  • Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F and Drabkin HA . (1998). Proc. Natl. Acad. Sci. USA, 95, 9572–9577.

  • Gleason D . (1977). Urologic Pathology M Tannenbaun (ed). Lea & Febiger: Philadelphia, pp. 171–197.

    Google Scholar 

  • Iseli C, Jongeneel CV and Bucher P . (1999). Proc. Int. Conf. Intell. Syst. Mol. Biol., 138–148.

  • Kampa D, Cheng J, Kapranov P, Yamanaka M, Brubaker S, Cawley S, Drenkow J, Piccolboni A, Bekiranov S, Helt G, Tammana H and Gingeras TR . (2004). Genome Res., 14, 331–342.

  • Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL, Fodor SP and Gingeras TR . (2002). Science, 296, 916–919.

  • Khochbin S and Lawrence JJ . (1989). EMBO J., 8, 4107–4114.

  • Kiyosawa H, Yamanaka I, Osato N, Kondo S and Hayashizaki Y . (2003). Genome Res., 13, 1324–1334.

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, GU J, Hood L and Rowen L, et al. (2001). Nature, 409, 860–921.

  • Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K and Ferrari M . (2004). Proc. Natl. Acad. Sci. USA, 101, 811–816.

  • Lee JT, Davidow LS and Warshawsky D . (1999). Nat. Genet., 21, 400–404.

  • Liu L, Yoon JH, Dammann R and Pfeifer GP . (2002). Oncogene, 21, 6835–6840.

  • Liu Y, Dehni G, Purcell KJ, Sokolow J, Carcangiu ML, Artavanis-Tsakonas S and Stifani S . (1996). Genomics, 31, 58–64.

  • McManus MT . (2003). Semin. Cancer Biol., 13, 253–258.

  • Nepveu A and Marcu KB . (1986). EMBO J., 5, 2859–2865.

  • Ramaswamy S, Ross KN, Lander ES and Golub TR . (2003). Nat. Genet., 33, 49–54.

  • Rinn JL, Euskirchen G, Bertone P, Martone R, Luscombe NM, Hartman S, Harrison PM, Nelson FK, Miller P, Gerstein M, Weissman S and Snyder M . (2003). Genes Dev., 17, 529–540.

  • Sanchez-Carbayo M, Socci ND, Charytonowicz E, Lu M, Prystowsky M, Childs G and Cordon-Cardo C . (2002). Cancer Res., 62, 6973–6980.

  • Shendure J and Church GM . (2002). Genome Biol., 3, research0044.1–research0044.14.

  • Shoemaker DD, Schadt EE, Armour CD, He YD, Garrett-Engele P, McDonagh PD, Loerch PM, Leonardson A, Lum PY, Cavet G, Wu LF, Altschuler SJ, Edwards S, King J, Tsang JS, Schimmack G, Schelter JM, Koch J, Ziman M, Marton MJ, Li B, Cundiff P, Ward T, Castle J, Krolewski M, Meyer MR, Mao M, Burchard J, Kidd MJ, Dai H, Phillips JW, Linsley PS, Stoughton R, Scherer S and Boguski MS . (2001). Nature, 409, 922–927.

  • Singh D, Febbo PG, Ross K, Jackson DG, Manola J, Ladd C, Tamayo P, Renshaw AA, D'Amico AV, Richie JP, Lander ES, Loda M, Kantoff PW, Golub TR and Sellers WR . (2002). Cancer Cell, 1, 203–209.

  • Sleutels F, Barlow DP and Lyle R . (2000). Curr. Opin. Genet. Dev., 10, 229–233.

  • Sorek R and Safer HM . (2003). Nucleic Acids Res., 31, 1067–1074.

  • Tamayo P, Slonim D, Mesirov J, Zhu Q, Kitareewan S, Dmitrovsky E, Lander ES and Golub TR . (1999). Proc. Natl. Acad. Sci. USA, 96, 2907–2912.

  • Tasheva ES and Roufa DJ . (1995). Genes Dev., 9, 304–316.

  • Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG and Higgs DR . (2003). Nat. Genet., 34, 157–165.

  • van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R and Friend SH . (2002). Nature, 415, 530–536.

  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J and Kalush F et al. (2001). Science, 291, 1304–1351.

  • Yelin R, Dahary D, Sorek R, Levanon EY, Goldstein O, Shoshan A, Diber A, Biton S, Tamir Y, Khosravi R, Nemzer S, Pinner E, Walach S, Bernstein J, Savitsky K and Rotman G . (2003). Nat. Biotechnol., 21, 379–386.

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Acknowledgements

The. authors are greatly indebted to H.A. Armelin for supporting this work, which is part of the Cooperation for Analysis of Gene Expression (CAGE) inter-departmental project that he coordinates. We thank E. Dias-Neto, R. R. Brentani and R. DeMarco for valuable suggestions and for critically reading the manuscript. E.M.R. is the recipient of a grant award from Coordenação de Aperfeiçoamento do Pessoal do Ensino Superior (CAPES). This work was financed by fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by a grant and fellowships from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP).

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, 05508-900, SP, Brazil

    Eduardo M Reis, Helder I Nakaya, Rodrigo Louro, Flavio C Canavez, Áurea V F Flatschart, Giulliana T Almeida, Camila M Egidio, Fernanda Festa, Denise Yamamoto, Renato Alvarenga, Camille C da Silva, Hamza El-Dorry, Mari C Sogayar, Aline M da Silva & Sergio Verjovski-Almeida

  2. Departamento de Bioquímica, Laboratório de Bioinformática, Instituto de Química, Universidade de São Paulo, São Paulo, 05508-900, SP, Brazil

    Eduardo M Reis, Apuã C Paquola, Abimael A Machado & Glauber C Brito

  3. Divisão de Oncologia, Hospital Israelita Albert Einstein, São Paulo, 05651-901, SP, Brazil

    Sérgio D Simon & Carlos A Moreira-Filho

  4. Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 05508-900, SP, Brazil

    Sérgio D Simon, Carlos A Moreira-Filho & Marcello A Barcinski

  5. Laboratório de Patologia Cirúrgica e Molecular, Hospital Sírio Libanês, São Paulo, 01308-050, SP, Brazil

    Katia R Leite & Luiz H Camara-Lopes

  6. Instituto Nacional de Cancer/MS, Rio de Janeiro, 20230-130, RJ, Brazil

    Franz S Campos, Etel Gimba, Giselle M Vignal & Marcello A Barcinski

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  1. Eduardo M Reis
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Correspondence to Sergio Verjovski-Almeida.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Reis, E., Nakaya, H., Louro, R. et al. Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer. Oncogene 23, 6684–6692 (2004). https://doi.org/10.1038/sj.onc.1207880

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