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Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (mRNA dataset)

ABSTRACT: BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to the DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on the HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA-mRNA relationships associated to the presence of the BRCA1 gene. Our results demonstrate that integration of mRNA and miRNA associated to BRCA1 expression was useful to discover new miRNA-gene interactions as molecular events underlying BRCA1-mediated tumorigenesis. Transcriptional profiling of the BRCA1-null HCC1937 cell line and HCC1937 cells after stable transfection of BRCA1. Two-condition experiment: Universal Human Reference RNA (Stratagene, catalog #740000) (Cy3) vs. cell line (Cy5). Biological replicates: 3 HCC1937, 3 BRCA1-transfected HCC1937 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Tanic M

PROVIDER: S-ECPF-GEOD-30821 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other

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Similar Datasets

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (miRNA dataset)

Project description:Microarray‐based techniques are being used to obtain miRNA and gene expression signatures associated with different samples. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from microarray experiments to obtain significant miRNA-mRNA relationships associated with the presence of the BRCA1 gene. We obtained significant miRNA-gene-pathway relationships underlying the array signatures. Furthermore, we have demonstrated that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, commonly regulate the TRAF2 gene, a key regulator of NF-κB and MAPK pathways. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-κB activity. Thus, integration between miRNA-mRNA expression data allowed us to define genes and pathways controlled by miRNAs induced in the context of BRCA1 expression. Comparison of miRNA expression profiles between two isogenic cell lines differing in BRCA1 gene expression status. Single-color experiments in a pairwise comparison design with three technical replicates per cell line.

| S-ECPF-GEOD-30763 | biostudies-other

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways

Project description:This SuperSeries is composed of the following subset Series: GSE30763: Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (miRNA dataset) GSE30821: Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (mRNA dataset) Refer to individual Series

| S-ECPF-GEOD-30822 | biostudies-other

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (mRNA dataset)

Project description:BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to the DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on the HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA-mRNA relationships associated to the presence of the BRCA1 gene. Our results demonstrate that integration of mRNA and miRNA associated to BRCA1 expression was useful to discover new miRNA-gene interactions as molecular events underlying BRCA1-mediated tumorigenesis.

2011-12-24 | GSE30821 | GEO

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (miRNA dataset)

2011-12-24 | GSE30763 | GEO

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (mRNA dataset)

2011-12-24 | E-GEOD-30821 | biostudies-arrayexpress

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways

Project description:This SuperSeries is composed of the SubSeries listed below.

2011-12-24 | GSE30822 | GEO

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (miRNA dataset)

Project description:Microarray?based techniques are being used to obtain miRNA and gene expression signatures associated with different samples. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from microarray experiments to obtain significant miRNA-mRNA relationships associated with the presence of the BRCA1 gene. We obtained significant miRNA-gene-pathway relationships underlying the array signatures. Furthermore, we have demonstrated that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, commonly regulate the TRAF2 gene, a key regulator of NF-?B and MAPK pathways. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-?B activity. Thus, integration between miRNA-mRNA expression data allowed us to define genes and pathways controlled by miRNAs induced in the context of BRCA1 expression. Comparison of miRNA expression profiles between two isogenic cell lines differing in BRCA1 gene expression status. Single-color experiments in a pairwise comparison design with three technical replicates per cell line.

2011-12-24 | E-GEOD-30763 | biostudies-arrayexpress

Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways

2011-12-24 | E-GEOD-30822 | biostudies-arrayexpress

miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators.

Project description:BackgroundTargeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance.MethodsThe miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy.ResultsmiR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor.ConclusionsDeregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract.

| S-EPMC7510138 | biostudies-literature

Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.

Project description:Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still not fully understood. We report here the involvement of miR-146a and miR-146b-5p that bind to the same site in the 3'UTR of BRCA1 and down-regulate its expression as demonstrated using reporter assays. This was further confirmed with the endogenous BRCA1 gene by transfecting microRNA (miRNA) precursors or inhibitors in mammary cell lines. This down-regulation was accompanied by an increased proliferation and a reduced homologous recombination rate, two processes controlled by BRCA1. Furthermore, we showed that the highest levels of miR-146a and/or miR-146b-5p are found in basal-like mammary tumour epithelial cell lines and in triple negative breast tumours, which are the closest to tumours arising in carriers of BRCA1 mutations. This work provides further evidence for the involvement of miRNAs in sporadic breast cancer through down-regulation of BRCA1.

| S-EPMC3377076 | biostudies-literature

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