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Regulatory consequences of ZNF395 knock-down in MDA-LM2-shTARBP2 cell-line

ABSTRACT: shRNA-mediated knock-down followed by transcriptomic profiling revealed that silencing of ZNF395 resulted in a significant up-regulation in several key oncogenes. ZNF395 was knocked-down, via expression of short-hairpin RNAs targeting its transcript. The cells were then subjected to transcripome profiling in comparison to mock-transfected cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Hani Goodarzi

PROVIDER: E-GEOD-49613 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.

Goodarzi Hani H Zhang Steven S Buss Colin G CG Fish Lisa L Tavazoie Saeed S Tavazoie Sohail F SF

Nature 20140709 7517

Aberrant regulation of RNA stability has an important role in many disease states. Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types. A defining feature of RNA is its ability to fold into structures. However, the roles of structural mRNA elements in cancer progression remain unexplored. Here we performed an unbiased search for post-transcriptional modula ...[more]

PMID: 25043050

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Regulatory consequences of TARBP2 knock-down in MDA-LM2 cell-line

Project description:siRNA-mediated knock-down followed by transcriptomic profiling revealed that silencing of TARBP2 resulted in a significant up-regulation of sRSE-carrying transcripts. Two independent siRNAs were used to knock down TARBP2 in metastatic MDA-LM2 cells. The cells were then subjected to transcripome profiling in comparison to mock-transfected cells.

2014-07-24 | E-GEOD-49611 | biostudies-arrayexpress

Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-07-16 | E-GEOD-49649 | biostudies-arrayexpress

Regulatory consequences of TARBP2 knock-down in MDA-LM2 cell-line [stability experiment]

Project description:siRNA-mediated knock-down followed by transcriptomic profiling revealed that silencing of TARBP2 resulted in a significant increase in the stability of sRSE-carrying transcripts. Two independent siRNAs were used to knock down TARBP2 in metastatic MDA-LM2 cells. The cells were then subjected to whole-genome transcript stabiliy measurements in comparison to mock-transfected cells.

2014-07-24 | E-GEOD-49612 | biostudies-arrayexpress

Regulatory consequences of SOX4 knock-down in MDA-LM2 cell line

Project description:Transcriptomic profiling of SOX4 knock-down MDA-LM2 cell line resulted in down-regulation of its transcriptional target gene, TMEM2. Two independent siRNAs were used to knock down SOX4 in metastatic MDA-LM2 cells. The cells were then subjected to transcripome profiling in comparison to control siRNA-transfected cells.

2016-03-15 | E-GEOD-79202 | biostudies-arrayexpress

Interaction between SNPs and DNA methylation affects gene expression in human brain

Project description:Gene expression is regulated by genetic variants and DNA methylation with evidence from molecular biology studies, as well as expression QTL (eQTL) mapping and methylation QTL (mQTL) mapping. In this study, we explored the interaction between genetic variants and DNA methylation for its influence on gene expression. We analyzed a postmortem brain data and identified 2,768 SNP-methylation interaction (SMI) that can survive Bonferroni correction for the number of tests in cis- region of each gene. Seven SNP-methylation pairs were significant after Bonferroni correction for all the tests, including number of gene expression traits, we performed in this study. Only a small proportion of the SMI had evidence from the exact same SNP-transcript pair in eQTL mapping or SNP-methylation pair in mQTL mapping. This suggested that the interaction analysis could uncover novel regulatory relationships, which would be missed by eQTL or mQTL analyses. Since methylation per se is regulated by both genetic and environmental factors, analysis indicates that the SMI detected in this study may involve both genetic and environmental regulation. A total of 155 postmortem cerebellum brains were used in this study, including 47 bipolar disorder, 46 schizophrenia, 15 depression patients and 47 normal controls. All were of European Ancestry. We also designed 13 random replicates in our experiment. Illumina Infinium HumanMethylation27 BeadChip was used for DNA methylation profiling. The assay was performed at the Genomics Core Facility at Northwestern University.

2013-06-30 | E-GEOD-38873 | biostudies-arrayexpress

Regulatory consequences of TARBP2 knock-down in MDA-LM2-shDicer cell-line

Project description:siRNA-mediated knock-down followed by transcriptomic profiling revealed that silencing of TARBP2 resulted in a significant up-regulation of sRSE-carrying transcripts. Two independent siRNAs were used to knock down TARBP2 in metastatic MDA-LM2 shDicer cells. The cells were then subjected to transcripome profiling in comparison to mock-transfected cells.

2014-07-24 | E-GEOD-56950 | biostudies-arrayexpress

Genome wide methylation array analysis in T-ALL

Project description:In short: Genome wide promoter DNA methylation profiling of 43 T-ALL samples and 5 T-cell controls (normal bone marrow and stimulated T-cells) . The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Manuscript abstract: Background: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. Design and Methods: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n=43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n= 32). Results: Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP- (low methylation). CIMP- T-ALL patients had significantly worse overall and event free survival (p=0.02 and p=0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. Conclusions: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2013-07-01 | E-GEOD-42079 | biostudies-arrayexpress

Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-01 | E-GEOD-42080 | biostudies-arrayexpress

Transcriptome-wide Regulation of Splicing and mRNA Localization by Muscleblind Proteins

Project description:The Muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in Myotonic Dystrophy (DM), where expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts using RNA sequencing and crosslinking/immunoprecipitation-sequencing approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function, in a pattern indicative of functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of sub-cellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs encoding membrane, synaptic and other proteins in both mouse and Drosophila cells, and Mbnls also contribute to protein secretion. These findings hold several new implications for DM pathogenesis. To assess global functions of Muscleblind proteins, RNA-Seq was performed using WT and Mbnl1 KO brain, heart, and muscle (5 mice each). Additionally, C2C12 mouse myoblasts were depleted of Mbnl1, Mbnl2, or both. Subcellular fractionation experiments were performed to analyze mRNA localization following depletion of Mbnl1 and Mbnl2 in C2C12 mouse myoblasts, and following depletion of Mbnl in Drosophila S-2R+ cells. CLIP-Seq was also performed against Mbnl1 in mouse brain, heart, muscle, and C2C12 myoblasts. Finally, ribosome footprinting was performed with C2C12 mouse myoblasts that were depleted of Mbnl1, Mbnl2, or both.

2012-08-17 | E-GEOD-39911 | biostudies-arrayexpress

Treatment of MM cells with IMiDs or reducing the expression of EIF2C2 significantly affects steady-state levels of miRNAs

Project description:Lenalidomide is a therapeutically active compound that binds to E3 ubiquitin ligase recruiter cereblon (CRBN) and induces cytotoxicity. We have identified eukaryotic translation initiation factor 2 subunit C2 (EIF2C2) as a new member of CRBN-downstream binding protein that plays an important role in microRNA (miRNA) maturation and function. The treatment of immunomodulatory drug (IMiD)-sensitive multiple myeloma (MM) cells with lenalidomide altered the steady-state levels of CRBN, EIF2C2 and miRNAs and induced apoptosis. However, although the treatment of IMiD-resistant MM cells with lenalidomide altered the steady-state levels of CRBN, EIF2C2 and miRNAs, but did not massively induce apoptosis. In contrast, silencing of EIF2C2 with its small hairpin RNA significantly altered the levels of miRNAs and induced apoptosis regardless of whether those cells are sensitive or resistant to IMiDs. Therefore, EIF2C2 could be considered as a new drug target for overcoming IMiDs resistance in MM cells. To find the role of EIF2C2 in MM cell growth, OCI-My5 cell lines My5/LV and My5/CRBN, with low and high CRBN expression, respectively, were treated 12 different ways. The steady-state levels of miRNAs between (1) My5/LV, EIF2C2-shRNA-treated My5/LV and EIF2C2-cDNA-treated My5/LV cells, (2) My5/CRBN, EIF2C2-shRNA-treated My5/CRBN and EIF2C2-cDNA-treated My5/CRBN cells, (3) My5/LV cells, My5/LV cells treated with 10 ÂµM lenalidomide for 72 hours or 120 hours, and EIF2C2-cDNA-treated My5/LV cells treated with 10 ÂµM lenalidomide for 72 hours, and (4) My5/CRBN cells, My5/CRBN cells treated with 10 ÂµM lenalidomide for 72 hours or 120 hours, and EIF2C2-cDNA-treated My5/CRBN cells treated with 10 ÂµM lenalidomide for 72 hours, were compared in this array.

2016-03-09 | E-GEOD-61693 | biostudies-arrayexpress

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