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Molecular Characterization of Breast Cancer Subtypes Derived from Joint Analysis of High Throughput miRNA and mRNA Data

ABSTRACT: MicroRNAs (miRNAs) are a class of short, single-stranded widely expressed noncoding RNAs that regulate the stability or translational efficiency of target messenger RNAs. Date derived from expression profiling of 489 miRNAs in 101 human primary breast tumor samples, along with genome-wide matched mRNA profiling and extensive clinical information were investigated in this study. miRNA and mRNA expression were analyzed using correlations and enrichments analyses. The results show that particular cellular processes such as proliferation, cell adhesion, and immune response are significantly enriched among genes with strong positive or negative correlation to individual or groups of miRNAs. Functional analyses were performed to validate the influence of miRNAs on proliferation. A group of miRNAs was identified that is associated to breast cancer disease free survival. This study provides a comprehensive dataset that can be used as groundwork for further studies of the involvement of miRNA in breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19536 | GEO | 2010/12/01

SECONDARY ACCESSION(S): PRJNA122257

REPOSITORIES: GEO

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Project description:In the present study we analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based Rotating Wall Vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1g-incubated ones. Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the most dysregulated. To improve the detection of functional miRNA-mRNA pairs we performed gene expression profiles on the same samples assayed for miRNA profiling and we integrated miRNA and mRNA expression data. The functional classification of miRNA-correlated genes evidenced significant enrichments in the biological processes of immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death and regulation of cell proliferation. We identified the correlation between miR-9-3p, miR-155-5p, miR-150-3p and miR-378-3p expression with that of genes involved in immune/inflammatory response (eg. IFNG and IL17F), apoptosis (eg. PDCD4 and PTEN) and cell proliferation (eg. NKX3-1 and GADD45A). Experimental assays of cell viability and apoptosis induction validated the results obtained by bioinformatics analyses demonstrating that in human PBLs the exposure to reduced gravitational force increases the frequency of apoptosis and decreases cell proliferation. microRNA expression profiling were carried out on total RNA extracted from PBLs of twelve healthy donors at the end of 24h-incubation time in MMG and in 1g conditions. Analyses were performed by using the M-bM-^@M-^\Human miRNA Microarray kit (V2)M-bM-^@M-^] (Agilent Technologies), that allows the detection of 723 known human (miRBase v.10.1) and 76 human viral miRNAs.By comparing the expression profile of MMG-incubated vs. 1g-incubated PBLs of the same donor, we found 42 differentially expressed miRNAs, 25 up-regulated and 17 down-regulated.

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Molecular Characterization of Breast Cancer Subtypes Derived from Joint Analysis of High Throughput miRNA and mRNA Data

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