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.