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MiRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.

ABSTRACT: INTRODUCTION:Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. METHODS:We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. RESULTS:We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. CONCLUSION:This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.

SUBMITTER: Enerly E

PROVIDER: S-EPMC3043070 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.

Enerly Espen E Steinfeld Israel I Kleivi Kristine K Leivonen Suvi-Katri SK Aure Miriam R MR Russnes Hege G HG Rønneberg Jo Anders JA Johnsen Hilde H Navon Roy R Rødland Einar E Mäkelä Rami R Naume Bjørn B Perälä Merja M Kallioniemi Olli O Kristensen Vessela N VN Yakhini Zohar Z Børresen-Dale Anne-Lise AL

PloS one 20110222 2

<h4>Introduction</h4>Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information.<h4>Methods</h4>We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We u ...[more]

PMID: 21364938

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Project description:BackgroundMerino sheep exhibit high wool production and excellent wool quality. The fleece of Merino sheep is predominantly composed of wool fibers grown from hair follicles (HFs). The HF is a complex biological system involved in a dynamic process governed by gene regulation, and gene expression is regulated by microRNAs (miRNAs). miRNA inhibits posttranscriptional gene expression by specifically binding to target messenger RNA (mRNA) and plays an important role in regulating gene expression, the cell cycle and biological development sequences. The purpose of this study was to examine mRNA and miRNA binding to identify key miRNAs and target genes related to HF development. This will provide new and important insights into fundamental mechanisms that regulate cellular activity and cell fate decisions within and outside of the skin.ResultsWe analyzed miRNA data in skin tissues collected from 18 Merino sheep on four embryonic days (E65, E85, E105 and E135) and two postnatal days (D7 and D30) and identified 87 differentially expressed miRNAs (DE-miRNAs). These six stages were further divided into two longer developmental stages based on heatmap cluster analysis, and the results showed that DE-mRNAs in Stage A were closely related to HF morphogenesis. A coanalysis of Stage A DE-mRNAs and DE-miRNAs revealed that 9 DE-miRNAs and 17 DE-mRNAs presented targeting relationships in Stage A. We found that miR-23b and miR-133 could target and regulate ACVR1B and WNT10A. In dermal fibroblasts, the overexpression of miR-133 significantly reduced the mRNA and protein expression levels of ACVR1B. The overexpression of miR-23b significantly reduced the mRNA and protein expression levels of WNT10A.ConclusionThis study provides a new reference for understanding the molecular basis of HF development and lays a foundation for further improving sheep HF breeding. miRNAs and target genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine-wool sheep.

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MiRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.

Publications

miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.

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