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Expression Profiling of Inflammatory Breast Cancer Cells Treated with the Novel Histone Deacetylase Inhibitor, CG-1521 (Affymetrix HuGene-1_0)

ABSTRACT: Studies of gene expression profiles using the whole genome wide microarray analysis in SUM149PT cells (ER-, p53mut) and SUM190PT cells (ER-, p53mut) when treated with 5 or 7.5 µM CG-1521 alone and in combination with 10 nM 17β-Estradiol. Comparisons between each treatment group provides evidence for the dysregulation of genes associated with the spindle assembly checkpoint.

ORGANISM(S): Homo sapiens

PROVIDER: GSE28542 | GEO | 2011/04/12

SECONDARY ACCESSION(S): PRJNA143031

REPOSITORIES: GEO

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Project description:In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the aggressiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in aggressive cell lines when compared to normal and less aggressive cell lines. Transient overexpression of miR-200c, miR-205, and miR-375 in MDA-MB-231 cells led to the inhibition of cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that it plays a more important role in regulating the aggressiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. To our knowledge, this study is the first systematic screening of functional miRNA target genes in aggressive breast cancer cells. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer aggressiveness and ultimately lead to the identification of novel biomarkers associated with prognosis. Affymetrix Gene 1.0 ST arrays were performed according to the manufacturer's directions on RNA extracted from breast cancer cell lines which are treated with miRNA mimic

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Expression Profiling of Inflammatory Breast Cancer Cells Treated with the Novel Histone Deacetylase Inhibitor, CG-1521 (Affymetrix HuGene-1_0)

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