Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer.
MicroRNAs are small noncoding RNAs that regulate the expression of protein-coding genes. To evaluate the involvement of microRNAs in prostate cancer, we determined genome-wide expression of microRNAs and mRNAs in 60 primary prostate tumors and 16 nontumor prostate tissues. The mRNA analysis revealed that key components of microRNA processing and several microRNA host genes, e.g., MCM7 and C9orf5, were significantly up-regulated in prostate tumors. Consistent with these findings, tumors expressed the miR-106b-25 cluster, which maps to intron 13 of MCM7, and miR-32, which maps to intron 14 of C9orf5, at significantly higher levels than nontumor prostate. The expression levels of other microRNAs, including a number of miR-106b-25 cluster homologues, were also altered in prostate tumors. Additional differences in microRNA abundance were found between organ-confined tumors and those with extraprostatic disease extension. Lastly, we found evidence that some microRNAs are androgen-regulated and that tumor microRNAs influence transcript abundance of protein-coding target genes in the cancerous prostate. In cell culture, E2F1 and p21/WAF1 were identified as targets of miR-106b, Bim of miR-32, and exportin-6 and protein tyrosine kinase 9 of miR-1. In summary, microRNA expression becomes altered with the development and progression of prostate cancer. Some of these microRNAs regulate the expression of cancer-related genes in prostate cancer cells.
Ambs
Stefan
S
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4258, USA. ambss@mail.nih.gov
Prueitt
Robyn L
RL
Yi
Ming
M
Hudson
Robert S
RS
Howe
Tiffany M
TM
Petrocca
Fabio
F
Wallace
Tiffany A
TA
Liu
Chang-Gong
CG
Volinia
Stefano
S
Calin
George A
GA
Yfantis
Harris G
HG
Stephens
Robert M
RM
Croce
Carlo M
CM
D000368:Aged; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D043244:Ribonuclease III / Q000378:metabolism; D015854:Up-Regulation
D035683:MicroRNAs; D012333:RNA, Messenger; D043244:Ribonuclease III