Project description:MicroRNA expression profiles can distinguish normal B cells from malignant B cells in chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. We evaluated the microRNA expression profiles of 94 samples of CLL cells for which ZAP-70 expression, mutations in the rearranged IgVH gene, and the time from diagnosis to initial treatment were known. We also investigated the presence of abnormalities in the genomic sequence of 42 microRNA genes.
Project description:MicroRNA expression profiles can distinguish normal B cells from malignant B cells in chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. We evaluated the microRNa expression profiles of 94 samples of CLL cells for which ZAP-70 expression; mutations in the rearranged IgVH gene; and the time from diagnosis to initial treatment were known. We also investigated the presence of abnormalities in the genomic sequence of 42 microRNA genes.
Project description:MicroRNAs are a class of small non-coding RNAs that control gene expression by targeting messenger RNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, microRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where microRNA signatures were associated with specific clinico-biological features. Here, we show that, in comparison to normal breast tissue, microRNAs are also aberrantly expressed in human breast cancer. The overall microRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated microRNAs being mir-125b, mir-145, mir-21, mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify microRNAs whose expression was correlated with specific breast cancer bio-pathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion or proliferation index.
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 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:We studied the value of the microRNAs as a signature for Chronic lymphocytic leukemia (CLL) patients with specific chromosomal abnormalities. We found that MiR-181b is abiomarker of disease progression in Chronic Lymphocytic Leukemia
Project description: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.
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:We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93,miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most upregulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells.