Dataset Information

MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

ABSTRACT: MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence-dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most noninvasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including miR-98/let-7), with most miRNA changes apparent already in the noninvasive carcinomas. In addition, patients that went on to develop metastasis showed increased expression of mir-423, and triple-negative breast carcinomas were most distinct from other tumor subtypes due to upregulation of the mir~17-92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested.

SUBMITTER: Farazi TA

PROVIDER: S-EPMC3129492 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

Farazi Thalia A TA Horlings Hugo M HM Ten Hoeve Jelle J JJ Mihailovic Aleksandra A Halfwerk Hans H Morozov Pavel P Brown Miguel M Hafner Markus M Reyal Fabien F van Kouwenhove Marieke M Kreike Bas B Sie Daoud D Hovestadt Volker V Wessels Lodewyk F A LF van de Vijver Marc J MJ Tuschl Thomas T

Cancer research 20110517 13

MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence-dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering b ...[more]

PMID: 21586611

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Project description:MicroRNAs (miRNAs) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 non-invasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed-sequence-dependent miRNA-target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most non-invasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including mir-98/let-7), with most miRNA changes apparent already in the non-invasive carcinomas. In addition, patients that went on to develop metastasis demonstrated increased expression of mir-423, and triple negative breast carcinomas were most distinct from other tumor subtypes due to up-regulation of the mir-17~92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible, but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested. 21 barcoded sequencing runs, including 185 unique samples and 54 samples in replicate (6 in triplicate and the remaining in duplicate). The details of each sample can be found in Supplementary Tables S1 and S2.

Project description:This SuperSeries is composed of the following subset Series: GSE29173: MicroRNA sequence and expression analysis in breast tumors by deep sequencing [miRNA sequence data] GSE29174: MicroRNA sequence and expression analysis in breast tumors by deep sequencing [mRNA expression array data] MicroRNAs (miRNAs) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 non-invasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed-sequence-dependent miRNA-target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most non-invasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including mir-98/let-7), with most miRNA changes apparent already in the non-invasive carcinomas. In addition, patients that went on to develop metastasis demonstrated increased expression of mir-423, and triple negative breast carcinomas were most distinct from other tumor subtypes due to up-regulation of the mir-17~92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible, but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested. Refer to individual Series

Project description:Wooden breast (WB) is a muscle disorder affecting modern commercial broiler chickens that leads to a palpable firm pectoralis major muscle and causes severe reduction in meat quality, resulting in substantial economic losses for the poultry industry. Most studies have focused on the regulatory mechanisms underlying this defect with respect to the gene and protein expression levels as well as the levels of metabolites. MicroRNAs (miRNAs) play critical roles in human muscular disorders, such as the Duchenne muscular dystrophy, by regulating the muscle regeneration or fibrosis processes. In this study, we investigated the miRNAs and related pathways that play important roles in the development of WB. We generated the miRNA expression profiles of the pectoralis major muscle samples from 3 WB-affected and 3 nonaffected chickens selected from a commercial broiler population via small RNA sequencing. A total of 578 miRNAs were identified in the chicken breast muscles from the initial analysis of the sequencing data. Of these, 23 miRNAs were significantly differentially expressed (false discovery rate [FDR] <0.05, log2|Foldchange| >1), including 20 upregulated and 3 downregulated miRNAs in the WB group compared to the normal group. Moreover, functional enrichment of the predicted target genes of differential miRNAs indicated that these miRNAs were involved in biological processes and pathways related to energy metabolism, apoptosis, focal adhesion, and development of blood vessels. Four differentially expressed miRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). We also highlighted several differentially expressed miRNAs, such as gga-miR-155, gga-miR-29c, and gga-miR-133, for their potential roles in the regulation of the development of WB. To the best of our knowledge, this is the first study investigating the miRNA expression profile of the breast muscle associated with WB. The findings of this study can be used to explore the potential molecular mechanisms of other muscle disorders in broilers and provide valuable information for chicken breeding.

Dataset Information

MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

Publications

MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

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