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 lias clearly emerged.
Original language | English (US) |
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Pages (from-to) | 6684-6692 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 23 |
Issue number | 39 |
DOIs | |
State | Published - Aug 26 2004 |
Externally published | Yes |
Keywords
- Antisense RNA
- Gleason score
- Intronic transcripts
- Microarray
- Prostate cancer
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research