Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways
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ABSTRACT: 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
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.
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.
2011-12-24 | GSE30763 | GEO
Project description: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: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: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:A long-prevailing model has held that the “seed” region (nucleotides 2-8) of a microRNA is typically sufficient to mediate target recognition and repression. However, numerous recent studies, both within the context of defining miRNA/target pairs by direct physical association and by directly assessing this model in vivo in C. elegans have brought this model into question. To test the importance of miRNA 3' pairing in vivo, in a mammalian system, we engineered a mutant murine mir-146a allele in which the 5' half of the mature microRNA retains the sequence of the wild-type mir-146a but the 3ʹ half has been altered to be anti-complementary to the wild-type miR-146a sequence. Mice homozygous or hemizygous for this mutant allele are phenotypically indistinguishable from wild-type controls and do not recapitulate any of the immunopathology previously described for mir-146a-null mice. Our results strongly support the conclusion that 3ʹ pairing is dispensable in the context of the function of a key mammalian microRNA.
Project description:Endothelial cells are critical for angiogenesis, and microRNAs plays important roles in this process. We investigated the regulatory role of microRNAs in endothelial cells of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly up-regulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion, and predicted a poorer prognosis. These results suggest that MiR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a may emerge as a potential anti-angiogenic target on ECs for HCC therapy. We have employed whole genome OneArray to examine the genome expression changes of HUVECs overexpressing miR-146a.
Project description:Endothelial cells are critical for angiogenesis, and microRNAs plays important roles in this process. We investigated the regulatory role of microRNAs in endothelial cells of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly up-regulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion, and predicted a poorer prognosis. These results suggest that MiR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a may emerge as a potential anti-angiogenic target on ECs for HCC therapy.
Project description:miR-146a is a known anti-inflammatory miRNA. Intringuigly, it is overexpressed in RAS-induced senescent cells which is accompanied with a rich pro-inflammatoy secretpry phenotype. We aim to study possible sponges for miR-146a.
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. 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.