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Comprehensive genomic profiling identified miRNA signatures associated with mammary tumor differentiation and development

ABSTRACT: We performed affymetrix gene expression profiling on mammary tumors from eight well-characterized genetically engineered Mouse (GEM) models of human breast cancer. The gene expression data will be combined with the miRNA gene expression data from the corresponding mammary tumors and tissues for integrated miRNA and mRNA gene expression analysis, which are useful in improving the identification of miRNA targets from potential targets identified in silico.

ORGANISM(S): Mus musculus

PROVIDER: GSE23938 | GEO | 2011/07/21

SECONDARY ACCESSION(S): PRJNA130315

REPOSITORIES: GEO

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Comprehensive genomic profiling identified miRNA signatures associated with mammary tumor differentiation and development

Project description:We performed affymetrix gene expression profiling on mammary tumors from eight well-characterized genetically engineered Mouse (GEM) models of human breast cancer. The gene expression data will be combined with the miRNA gene expression data from the corresponding mammary tumors and tissues for integrated miRNA and mRNA gene expression analysis, which are useful in improving the identification of miRNA targets from potential targets identified in silico. mRNA expression data for 41 mouse primary mammary tumors and 5 mouse normal mammary glands

2011-07-20 | E-GEOD-23938 | biostudies-arrayexpress

Genomic Profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage (primary tumors and normal mammary glands)

Project description:MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in many human diseases including breast cancer. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the roles of miRNAs in association with oncogenic drivers and in specifying sub-types of breast cancer, we performed miRNAexpression profiling on mammary tumors from eight well-characterized genetically -engineered Mouse (GEM) models of human breast cancer including MMTV–H-Ras, -Her2/neu, -c-Myc, -PymT, –Wnt1 and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1fl/fl;p53+/-;MMTV-cre and the p53fl/fl ;MMTV-cre transplant model. miRNA expression data for 41 mouse primary mammary tumors and 5 mouse normal mammary glands

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Genomic Profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage (mammary normal and tumors in different mice strains)

Project description:MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in many human diseases including breast cancer. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the roles of miRNAs in association with oncogenic drivers and in specifying sub-types of breast cancer, we performed miRNAexpression profiling on mammary tumors from eight well-characterized genetically -engineered Mouse (GEM) models of human breast cancer including MMTV–H-Ras, -Her2/neu, -c-Myc, -PymT, –Wnt1 and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1fl/fl;p53+/-;MMTV-cre and the p53fl/fl ;MMTV-cre transplant model. As supplementary data miRNA expression data for 3 mouse primary mammary tumors and 8 mouse normal mammary glands from different mouse strains

2011-07-20 | E-GEOD-23977 | biostudies-arrayexpress

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Sensitivity of cholangiocarcinoma cells to gemcitabine is affected by microRNA expression

Project description:We examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. Two intrahepatic CCA cell lines, HuH28 and HuCCT1 were used. HuCCT1 cells were more sensitive to Gem than were HuH28 cells. The miRNA expression profiles of HuH28 and HuCCT1 were determined by microarray analysis. Eighteen miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221) restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment.

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Breast Cancer Cell Secretome Analysis to Decipher miRNA Tumor Biology and Discover Potential Biomarkers

Project description:MicroRNA (miRNA/miR) miR526b and miR655 overexpressed tumor cell-free secretions promote breast cancer phenotypes in the tumor microenvironment (TME). However, the mechanisms of miRNA regulating TME have never been investigated. With mass spectrometry analysis of MCF7-miRNA-overexpressed versus miRNA-low MCF7-Mock tumor cell secretomes, we identified 34 novel secretory proteins coded by eight genes YWHAB, TXNDC12, MYL6B, SFN, FN1, PSMB6, PRDX4, and PEA15 those are differentially regulated. We used bioinformatic tools and systems biology approaches to identify these markers’ role in breast cancer. Gene ontology analysis showed that the top functions are related to apoptosis, oxidative stress, membrane transport, and motility, supporting miRNA-induced phenotypes. These secretory markers expression is high in breast tumors, and a strong positive correlation exists between upregulated markers’ mRNA expressions with miRNA cluster expression in luminal A breast tumors. Gene expression of secretome markers is higher in tumor tissues compared to normal samples, and immunohistochemistry data supported gene expression data. Moreover, both up and downregulated marker expressions are associated with breast cancer patient survival. miRNA regulates these marker protein expressions by targeting transcription factors of these genes. Premature miRNA (pri-miR526b and pri-miR655) are established breast cancer blood biomarkers. Here we report novel secretory markers upregulated by miR526b and miR655 (YWHAB, MYL6B, PSMB6, and PEA15) are significantly upregulated in breast cancer patients’ plasma, and are potential breast cancer biomarkers.

2023-05-10 | PXD031771 | Pride

Identification of microRNA targets in the mammalian inner ear using a comprehensive transcriptome and proteome integrated approach

Project description:We have employed a novel approach for the identification of functionally important microRNA (miRNA)-target interactions using integrated miRNA, transcriptome and proteome profiles with advanced in silico analysis. By looking at both the transcript and protein levels of expression, a thorough coverage of miRNA regulation was obtained. Microdissected auditory and vestibular sensory epithelia were used as the model system, thus being the first time such a comparison was carried out in a neuroepithelial system. Moreover, this is one of only a few studies employing proteome screening for the identification of miRNA targets. Notably, this approach can be employed for the study of other tissues and organs. We detected the expression of 157 miRNAs in the inner ear sensory epithelia, with 53 miRNAs differentially expressed between the cochlea and vestibule. By searching for enrichment and depletion of miRNA targets in the transcript and protein datasets with a reciprocal or similar expression, respectively, as the regulatory miRNA, we identified functionally important miRNAs. Finally, the interaction between miR-135b and PSIP1-P75, a transcriptional coacitvator previously unknown in the inner ear, was identified and validated experimentally. We suggest that miR-135b may serve as a cellular effector, involved in regulating some of the differences between the cochlear and vestibular hair cells.

2011-04-20 | GSE23081 | GEO

Genomic Profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage (primary tumors and normal mammary glands)

2011-07-21 | GSE23978 | GEO

Genomic Profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage (mammary normal and tumors in different mice strains)

2011-07-21 | GSE23977 | GEO

Integrated SV40 T/t-antigen Cancer Signature in Aggressive Breast, Prostate and Lung Carcinomas with Poor Prognosis 2

Project description:Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based upon their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simean virus 40 T/t-antigens that is associated with the biologic behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb or BRCA1 expression, but not in tumors initiated through the overexpression of myc, ras, her2/neu, or Polyoma middle T oncogenes. Importantly, human breast, lung and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Since this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Since the these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in pre-clinical testing of therapies focused on these biologically important targets. Keywords: Genetically engineered mouse (GEM) models of cancer, epithelial carcinoma, SV40 T/t-antigen, survival predictor

2007-09-01 | GSE8663 | GEO

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