TY - JOUR
T1 - Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer
AU - Reis, Eduardo M.
AU - Nakaya, Helder I.
AU - Louro, Rodrigo
AU - Canavez, Flavio C.
AU - Flatschart, Áurea V.F.
AU - Almeida, Giulliana T.
AU - Egidio, Camila M.
AU - Paquola, Apuã C.
AU - Machado, Abimael A.
AU - Festa, Fernanda
AU - Yamamoto, Denise
AU - Alvarenga, Renato
AU - Da Silva, Camille C.
AU - Brito, Glauber C.
AU - Simon, Sérgio D.
AU - Moreira-Filho, Carlos A.
AU - Leite, Katia R.
AU - Camara-Lopes, Luiz H.
AU - Campos, Franz S.
AU - Gimba, Etel
AU - Vignal, Giselle M.
AU - El-Dorry, Hamza
AU - Sogayar, Mari C.
AU - Barcinski, Marcello A.
AU - Da Silva, Aline M.
AU - Verjovski-Almeida, Sergio
N1 - Funding Information:
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 Coordenac¸ão de Aperfeic¸oamento 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 Fundac¸ão de Amparo a Pesquisa do Estado de São Paulo (FAPESP).
PY - 2004/8/26
Y1 - 2004/8/26
N2 - 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 lias clearly emerged.
AB - 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 lias clearly emerged.
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U2 - 10.1038/sj.onc.1207880
DO - 10.1038/sj.onc.1207880
M3 - Article
C2 - 15221013
AN - SCOPUS:4444364003
SN - 0950-9232
VL - 23
SP - 6684
EP - 6692
JO - Oncogene
JF - Oncogene
IS - 39
ER -