TIA proteins drives global and specific translational repression of genes linked to the cell-cycle progression and DNA replication/repair
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54540 | GEO | 2015/05/19
SECONDARY ACCESSION(S): PRJNA237007
REPOSITORIES: GEO
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Project description:The reduction of T-cell intracellular antigen (TIA) proteins in transformed cells leads to the acquisition of aberrant cellular phenotypes promoting uncontrolled cell proliferation and tumor growth. Here we show that global and specific translational rates are regulatory gene events that contribute markedly to the acquisition of above cellular phenotypes. For example, we observe a significant increase of ribosomal population and translational machinery components in TIA-reduced HeLa cells. Polysomal microarray analysis shows specific changes at both the transcript and translational level following TIA reduction, identifying translationally regulated mRNAs that are not transcriptionally regulated which seem to be prevalent for the adaptation to the new environmental conditions. Validation of microarray data using RT-QPCR and immunological analysis for representative genes were carried out. Up-regulated in this class of mRNA are those involved in cell-cycle progression and DNA replication/repair, including several mRNAs with specific sequences to bind TIA proteins. Our data support a hypothesis that a concerted activation of both global and selective translational rates is relevant for the transition from quiescent to proliferative status in TIA-depleted HeLa cells. Two independent replicates were performed for each experimental condition and hybridized to SurePrint G3 Human GE 8x60K Agilent microarrays.
2015-05-19 | E-GEOD-54540 | biostudies-arrayexpress
Project description:Background: T-cell intracellular antigen (TIA) proteins function as regulators of cell homeostasis. These proteins control gene expression globally at multiple levels in response to dynamic regulatory changes and environmental stresses. Herein we identified a micro(mi)RNA signature associated to transiently TIA-depleted HeLa cells and analyzed the potential role of miRNAs combining genome-wide analysis data on mRNA and miRNA profiles. Results: Using high-throughput miRNA expression profiling, transient depletion of TIA-proteins in HeLa cells was observed to promote significant and reproducible changes (>2-fold, FDR<0.0001) affecting to a pool of up-regulated miRNAs (miR-30b*, miR125a-3p, miR-193a-5p, miR-197_MM2, miR-203, miR-210, miR-371-5p, miR-373*, miR-483-5p, miR-492, miR-498, miR-503, miR-572, miR-586, miR-612, miR-615, miR-623, miR-625, miR-629, miR-638, miR-658, miR-663, miR-671, miR-769-3p and miR-744). Differential expression analysis of some miRNAs was validated by reverse transcription and real time PCR. By target prediction and combined analysis of the genome-wide expression profiles of the mRNAs and miRNAs identified in TIA-depleted HeLa cells, we detected concomitant connections between up-regulated miRNAs and putative and experimental targeted mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database analyses suggest that targeted mRNAs are related with biological processes associated to the regulation of DNA-dependent transcription, signal transduction and multicellular organismal development as well as with the enrichment of pathways in cancer, focal adhesion, regulation of actin cytoskeleton and MAPK and Wnt signalling pathways, respectively. Conclusion: All this considered, these observations suggest that specific miRNAs could act as potential mediators of the epigenetic switch linking transcriptomic dynamics and cell phenotypes mediated by TIA proteins.
2013-02-06 | GSE41213 | GEO
Project description:Background: T-cell intracellular antigen (TIA) proteins function as regulators of cell homeostasis. These proteins control gene expression globally at multiple levels in response to dynamic regulatory changes and environmental stresses. Herein we identified a micro(mi)RNA signature associated to transiently TIA-depleted HeLa cells and analyzed the potential role of miRNAs combining genome-wide analysis data on mRNA and miRNA profiles. Results: Using high-throughput miRNA expression profiling, transient depletion of TIA-proteins in HeLa cells was observed to promote significant and reproducible changes (>2-fold, FDR<0.0001) affecting to a pool of up-regulated miRNAs (miR-30b*, miR125a-3p, miR-193a-5p, miR-197_MM2, miR-203, miR-210, miR-371-5p, miR-373*, miR-483-5p, miR-492, miR-498, miR-503, miR-572, miR-586, miR-612, miR-615, miR-623, miR-625, miR-629, miR-638, miR-658, miR-663, miR-671, miR-769-3p and miR-744). Differential expression analysis of some miRNAs was validated by reverse transcription and real time PCR. By target prediction and combined analysis of the genome-wide expression profiles of the mRNAs and miRNAs identified in TIA-depleted HeLa cells, we detected concomitant connections between up-regulated miRNAs and putative and experimental targeted mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database analyses suggest that targeted mRNAs are related with biological processes associated to the regulation of DNA-dependent transcription, signal transduction and multicellular organismal development as well as with the enrichment of pathways in cancer, focal adhesion, regulation of actin cytoskeleton and MAPK and Wnt signalling pathways, respectively. Conclusion: All this considered, these observations suggest that specific miRNAs could act as potential mediators of the epigenetic switch linking transcriptomic dynamics and cell phenotypes mediated by TIA proteins. The analysis includes two cell types. Three biological replicates were performed per cell type and they were compared by using three dual-channel microarray hybridizations.
2013-02-06 | E-GEOD-41213 | biostudies-arrayexpress
Project description:The knock down of T-cell intracellular antigen (TIA) proteins enhances the acquisition of aberrant cellular phenotypes promoting uncontrolled cell and tumor growth. Hereby, we report that inducible expression of either TIA1 or TIAR in human embryonic kidney (HEK293) cells represses cell proliferation. Mechanistically, the sustained expression of either TIA1 or TIAR protein abolishes endogenous TIA1/TIAR protein expression via regulating splicing of their own pre-mRNAs. This event is concomitant with cell cycle arrest and cell death by apoptosis. Based on genome-wide analysis of the transcript expression patterns in HuR-, TIA1- or TIAR-expressing HEK293 cells, we found regulatory links among the up-regulation on a select subset of p53 pathway genes involved in G1/S cell-cycle and apoptosis control. Finally, nude mice injected with TIA1- or TIAR-expressing HEK293 cells decrease, and even abolishing, the growth of tumor xenografts relative to control cells. Collectively, these observations show that TIA proteins can function as tumor suppressor genes.
2015-03-05 | GSE51500 | GEO
Project description:Analysis of gene expression profiles during the course of both TIA-1 and TIAR expression suppression in HeLa cells
2009-02-27 | E-MTAB-93 | biostudies-arrayexpress
Project description:Background: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells.
2014-11-19 | GSE47664 | GEO
Project description:The knock down of T-cell intracellular antigen (TIA) proteins enhances the acquisition of aberrant cellular phenotypes promoting uncontrolled cell and tumor growth. Hereby, we report that inducible expression of either TIA1 or TIAR in human embryonic kidney (HEK293) cells represses cell proliferation. Mechanistically, the sustained expression of either TIA1 or TIAR protein abolishes endogenous TIA1/TIAR protein expression via regulating splicing of their own pre-mRNAs. This event is concomitant with cell cycle arrest and cell death by apoptosis. Based on genome-wide analysis of the transcript expression patterns in HuR-, TIA1- or TIAR-expressing HEK293 cells, we found regulatory links among the up-regulation on a select subset of p53 pathway genes involved in G1/S cell-cycle and apoptosis control. Finally, nude mice injected with TIA1- or TIAR-expressing HEK293 cells decrease, and even abolishing, the growth of tumor xenografts relative to control cells. Collectively, these observations show that TIA proteins can function as tumor suppressor genes. Two independent biological replicates were performed per sample type. Agilent SurePrint G3 Human Gene Expression 8x60K v2 array were used in all cases (single-channel hybridizations)
2015-03-05 | E-GEOD-51500 | biostudies-arrayexpress
Project description:Background: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells. For each cell type, three biological replicates were prepared and hybridized to Affymetrix GeneChips (HG U133plus2). 3+3 hybridizations in total for a single comparison KO vs WT.
2014-11-19 | E-GEOD-47664 | biostudies-arrayexpress
Project description:This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1- and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenotypes. The data of differential expression were validated by using genome-wide microarrays and QPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Taken together, these results indicate that differential gene expression, alternative pre-mRNA isoforms, promoter usage and microRNA profiling contribute to define the molecular expression phenotypes implied in the progression of proliferative phenotypes associated to the absence of TIA proteins and prioritize candidates for future study. Each library was run on one RNASeq Multiplex of 76 bp using sequencing from Illumina Genome Analyzer (GAIIx). Three samples were analyzed in this manner, taken from control, TIA1 and TIAR shRNA-depleted HeLa cells.
2014-11-19 | E-GEOD-46516 | biostudies-arrayexpress
Project description:This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1- and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenotypes. The data of differential expression were validated by using genome-wide microarrays and QPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Taken together, these results indicate that differential gene expression, alternative pre-mRNA isoforms, promoter usage and microRNA profiling contribute to define the molecular expression phenotypes implied in the progression of proliferative phenotypes associated to the absence of TIA proteins and prioritize candidates for future study.
2014-11-19 | GSE46516 | GEO