title: The miR-15a-miR-16-1 locus is homozygously deleted in a subset of prostate cancers.
abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate the expression of protein coding genes. In this study, we screened highly informative prostate cancer cell lines and xenografts (n = 42) for miRNA gene copy number and expression changes. The expression profiling showed distinction between cell lines and xenografts as well as between androgen sensitive and independent models. Only a few copy number alterations that were associated with expression changes were identified. Most importantly, the miR-15a-miR-16-1 locus was found to be homozygously deleted in two samples leading to the abolishment of miR-15a, but not miR-16, expression. miR-16 is also expressed from another genomic locus. Mutation screening of the miR-15a-miR-16-1 gene in the model systems as well as clinical samples (n = 50) revealed no additional mutations. In conclusion, our data indicate that putative tumor suppressors, miR-15a and miR-16-1, are homozygously deleted in a subset of prostate cancers, further suggesting that these miRNAs could be important in the development of prostate cancer.
authors.affiliation: Institute of Medical Technology, University of Tampere, Tampere University Hospital, Finland.
authors.forename: Kati P
authors.initials: KP
authors.lastname: Porkka
authors.forename: Erinn-Lee
authors.initials: EL
authors.lastname: Ogg
authors.forename: Outi R
authors.initials: OR
authors.lastname: Saramäki
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Heidi
authors.initials: H
authors.lastname: Pukkila
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.forename: Wytske M
authors.initials: WM
authors.lastname: van Weerden
authors.forename: Maija
authors.initials: M
authors.lastname: Wolf
authors.forename: Olli P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
mesh_terms: D045744:Cell Line, Tumor; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D017353:Gene Deletion; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006720:Homozygote; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs