In silico prediction and experimental validation of natural antisense transcripts in two cancer-associated regions of human chromosome 6.
Antisense transcription has long been recognized as a mechanism involved in the regulation of gene expression. Therefore, several human diseases associated with abnormal patterns of gene expression might display antisense RNA-mediated pathogenetic mechanisms. Such issue could be particularly relevant for cancer pathogenesis, since deregulated gene expression has long been established as a hallmark of cancer cells. Herein, we report on a bioinformatic search for antisense transcription in two cancer-associated regions of human chromosome 6 (6q21 and 6q27). Natural antisense transcripts (NATs) for several genes in both genomic regions were predicted in silico and subsequently validated by strand-specific RT-PCR. Detailed experimental validation by quantitative real-time RT-PCR of five putative cancer related sense-antisense transcript pairs revealed a single candidate tumor suppressor gene (RPS6KA2) whose expression levels display marked cancer-related changes that are likely mediated by its antisense RNA in a breast cancer cell line model.
Monti
Laura
L
Department of Biotechnology and Molecular Sciences, University of Insubria, I-21100 Varese, Italy.
Cinquetti
Raffaella
R
Guffanti
Alessandro
A
Nicassio
Francesco
F
Cremona
Mattia
M
Lavorgna
Giovanni
G
Bianchi
Fabrizio
F
Vignati
Francesca
F
Cittaro
Davide
D
Taramelli
Roberto
R
Acquati
Francesco
F
D002896:Chromosomes, Human, Pair 6; D019295:Computational Biology / Q000379:methods; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006801:Humans; D007438:Introns; D008954:Models, Biological; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000096:biosynthesis / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D016372:RNA, Antisense; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3