| Experiment ID | EXP00129 |
| Reference | Title: Expression of microRNA and their gene targets are dysregulated in preinvasivebreast cancer. Author: Hannafon BN, Sebastiani P, de las Morenas A, Lu J, Rosenberg CL. Journal: Breast Cancer Res. 2011 Mar 4;13(2):R24. doi: 10.1186/bcr2839. Abstract: INTRODUCTION: microRNA (miRNA) are short, noncoding RNA that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in early stages, wehypothesized that miRNA expression dysregulation and the predicted changes ingene expression might also be found in early breast neoplasias.METHODS: Expression profiling of 365 miRNA by real-time quantitative polymerasechain reaction assay was combined with laser capture microdissection to obtain anepithelium-specific miRNA expression signature of normal breast epithelium fromreduction mammoplasty (RM) (n = 9) and of paired samples of histologically normalepithelium (HN) and ductal carcinoma in situ (DCIS) (n = 16). To determine howmiRNA may control the expression of codysregulated mRNA, we also performed geneexpression microarray analysis in the same paired HN and DCIS samples andintegrated this with miRNA target prediction. We further validated several targetpairs by modulating the expression levels of miRNA in MCF7 cells and measured theexpression of target mRNA and proteins.RESULTS: Thirty-five miRNA were aberrantly expressed between RM, HN and DCIS.Twenty-nine miRNA and 420 mRNA were aberrantly expressed between HN and DCIS.Combining these two data sets with miRNA target prediction, we identified twoestablished target pairs (miR-195:CCND1 and miR-21:NFIB) and tested several novelmiRNA:mRNA target pairs. Overexpression of the putative tumor suppressormiR-125b, which is underexpressed in DCIS, repressed the expression of MEMO1,which is required for ErbB2-driven cell motility (also a target of miR-125b), andNRIP1/RIP140, which modulates the transcriptional activity of the estrogenreceptor. Knockdown of the putative oncogenic miRNA miR-182 and miR-183, bothhighly overexpressed in DCIS, increased the expression of chromobox homolog 7(CBX7) (which regulates E-cadherin expression), DOK4, NMT2 and EGR1. Augmentationof CBX7 by knockdown of miR-182 expression, in turn, positively regulated theexpression of E-cadherin, a key protein involved in maintaining normal epithelialcell morphology, which is commonly lost during neoplastic progression.CONCLUSIONS: These data provide the first miRNA expression profile of normalbreast epithelium and of preinvasive breast carcinoma. Further, we demonstratethat altered miRNA expression can modulate gene expression changes thatcharacterize these early cancers. We conclude that miRNA dysregulation likelyplays a substantial role in early breast cancer development. PMID: 21375733 |
| Expressiion Profile | Description: Expression of microRNAs and their gene targets are dysregulated in pre-invasive breast cancer (microRNA) Organism: Homo sapiens GEO ID: GSE24508 Platform: GPL10349 Number of samples: 19 |
| Design and Sample | Cancer Type: breast cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: ductal carcinoma in situ Control Sample: normal breast epithelium Num of Case: 8 Num of Control: 8 Quantification Software: Limma Num of miRNAs: 209 |
| Identification | Num of Up: 12 Num of Down: 12 |