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

• Published in: Oncogene Vol. 23; no. 39; pp. 6684 - 6692
• Main Authors: REIS, Eduardo M, NAKAYA, Helder I, YAMAMOTO, Denise, ALVARENGA, Renato, DA SILVA, Camille C, BRITO, Glauber C, SIMON, Sérgio D, MOREIRA-FILHO, Carlos A, LEITE, Katia R, CAMARA-LOPES, Luiz H, CAMPOS, Franz S, GIMBA, Etel, LOURO, Rodrigo, VIGNAL, Giselle M, EL-DORRY, Hamza, SOGAYAR, Mari C, BARCINSKI, Marcello A, DA SILVA, Aline M, VERJOVSKI-ALMEIDA, Sergio, CANAVEZ, Flavio C, FLATSCHART, Aurea V. F, ALMEIDA, Giulliana T, EGIDIO, Camila M, PAQUOLA, Apua C, MACHADO, Abimael A, FESTA, Fernanda
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 26-08-2004; Nature Publishing Group
• Subjects: Antisense RNA; Biological and medical sciences; Cell Differentiation - genetics; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA microarrays; Exons; Fundamental and applied biological sciences. Psychology; Genomes; Gynecology. Andrology. Obstetrics; Humans; Introns; Male; Male genital diseases; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Nephrology. Urinary tract diseases; Polymerase Chain Reaction; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; RNA, Antisense - genetics; RNA, Antisense - metabolism; Transcription; Transcriptomes; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Gleason score; Urinary system disease; Prostate disease; intronic transcripts; Antisense RNA; Malignant tumor; Differentiation; Gene expression; Microarray; Male genital diseases; Carcinogenesis; Prostate cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207880

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< or =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.