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Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer.

ABSTRACT: 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.

SUBMITTER: Ambs S

PROVIDER: S-EPMC2597340 | biostudies-other | 2008 Aug

REPOSITORIES: biostudies-other

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Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer.

Ambs Stefan S 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

Cancer research 20080801 15

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 ...[more]

PMID: 18676839

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Project description:MicroRNAs are small non-coding RNAs that regulate mRNA function. Recent studies have shown that microRNA expression is altered in tumors. We studied the expression of both microRNAs and mRNAs in 60 primary prostate tumors and 16 non-tumor prostate tissues to evaluate the involvement of microRNAs in prostate cancer. Global microRNA expression was determined in RNA isolated from fresh-frozen human tissues with a custom oligonucleotide microarray chip. Expression analysis of mRNAs using Affymetrix gene chips revealed that Dicer, a key component of microRNA processing, and two microRNA host genes, MCM7 and C9orf5, were significantly up-regulated in prostate tumors. Consistent with the findings, tumors expressed at higher levels the miR-25 cluster (miR-25/miR-93/miR-106b), which maps to intron 13 of MCM7, and miR-32, which maps to intron 14 of C9orf5, than non-tumor prostate tissues. Other microRNAs that were overexpressed included miR-26a, miR-31, miR-182, miR-196a, and miR-200c, among others, and homologues of the miR-25 cluster, such as miR-92 and miR-106a. Among the down-regulated microRNAs in tumors were the miR-1/miR-133a cluster, miR-490, miR-494 and miR-520h. Differences in microRNA expression were also observed between high and low Gleason score and between tumors that either showed or did not show extraprostatic extension. A 37-probeset signature, representing 23 different mature microRNAs, correctly classified all non-tumor tissues and 80% of the tumors. In summary, our data indicate that alterations in microRNA expression occur in the development and progression of human prostate cancer. Such changes may prove useful in the development of novel diagnostic and prognostic markers. Keywords: Marcodissected tissues Sixty fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the frozen specimens. Surrounding non-tumor prostate tissue was collected from 16 patients with prostate cancer. All tissues were collected between 2002 and 2004. Information on race/ethnicity was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire (UMD). Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. The study was approved by the institutional review boards of the participating institutions. Total RNA was isolated using the TRIZOL reagent according to the manufacturer’s instructions (Invitrogen, Carlsbad, CA). RNA integrity for each sample was confirmed with the Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Each RNA was then split into two pools that were either processed for the microRNA microarray or the mRNA microarray.

Dataset Information

Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer.

Publications

Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer.

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