MicroRNA profiling of human normal prostate and prostate cancer samples to investigate the role of miRNA involvement in prostate carcinogenesis
ABSTRACT: MicroRNA (miRNA) expression profiles for prostate cancers were examined to investigate the miRNA involvement in prostate carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate prostate cancers from noncancerous prostate tissues.
Proceedings of the National Academy of Sciences of the United States of America 20060203 7
Small noncoding microRNAs (miRNAs) can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. From a large-scale miRnome analysis on 540 samples including lung, breast, stomach, prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA signature composed by a large portion of overexpressed miRNAs. Among these miRNAs are some with well characterized cancer association, such as miR-17-5p, miR-20a, miR-21, miR-92, miR-106a, ...[more]
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.
Project description:MicroRNA (miRNA) expression profiles for gastric cancers were examined to investigate the miRNA involvement in stomach carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate stomach cancers from noncancerous stomach tissues.
Project description:MicroRNA (miRNA) expression profiles for colon cancers were examined to investigate the miRNA involvement in colon carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate colon cancers from noncancerous colon tissues.
Project description:MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate the miRNA involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues.
Project description:MicroRNA (miRNA) expression profiles for pancreatic endocrine tumors were examined to investigate the miRNA involvement in pancreatic carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate pancreatic cancers from noncancerous pancreas tissues.
Project description:MicroRNA expression profiles in response to LBH589 were examined in order to identify HDACi-induced alterations in miRNA expression that regulate apoptotic signaling in chronic lymphocytic leukemia.plasia. miRNA microarray analysis identified unique alterations in miRNA profile that could be used to identify new pathways for apoptosis regulation in CLL.
Project description:MicroRNA miRNA expression profiles for human ovarian carcinomas were examined to investigate the miRNA involvement in the development of this neoplasia. miRNA microarray analysis identified statistical unique profiles, which could discriminate ovarian carcinomas from noncancerous ovarian tissues, and different groups of tumors classified according to histo-pathological characteristics.
Project description:MicroRNA miRNA expression profiles for human HeLa cells (Cervical cancer), overexpressing p19 H-Ras, were examined to investigate the miRNA regulation by p19 H-Ras. miRNA microarray analysis identified statistical unique profiles, which could discriminate miRNAs regulated by p19 H-Ras and not regulated by the p19 mutant (W164A) H-Ras.
Project description:Background. Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results. We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusions. This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.