This SuperSeries is composed of the SubSeries listed below.
Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging.
Age, Specimen part
View Samples5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA expression. In addition, it has been reported that 5-FU incorporates into the RNAs constituting the translational machinery and that 5-FU affects the amount of some mRNAs associated with ribosomes. However, the impact of 5-FU on translational regulation remains unclear. Using translatome profiling, we report that a clinically relevant dose of 5-FU induces a translational reprogramming in colorectal cancer cell lines. Comparison of mRNA distribution between polysomal and non-polysomal fractions in response to 5-FU treatment using microarray quantification identified 313 genes whose translation was selectively regulated. These regulations were mostly stimulatory (91%). Among these genes, we showed that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription factor whose translation in normal condition is known to be inhibited by mir-155. In response to 5-FU, the expression of mir-155 decreases thus stimulating the translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific mRNA translation was associated with reduction of global protein synthesis. Altogether, these findings indicate that 5-FU promotes a translational reprogramming leading to the increased translation of a subset of mRNAs that involves at least for some of them, miRNA-dependent mechanisms. This study supports a still poorly evaluated role of translational control in drug response.
Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism.
Treatment
View SamplesWe differentiated the murine IDG-SW3 cell line for 28 days until the cells displayed a mature osteocyte-like phenotype. Triplicate cultures of the IDG-SW3 cells were then treated with 50nM PTH (1-34) or vehicle control (PBS) for 24 hours. RNA was harvested from the cultures and used to perform RNA Seq analysis. We found that many genes previously shown to be markers of the osteocyte phenotype were strongly downregulated in response to PTH treatment. Furthermore, we found that genes known to inhibit cell motility were downregulated in response to PTH, whereas genes promoting motility were upregulated. This corresponds to the increased cell motility observed in PTH-treated IDG-SW3 cell cultures. Therefore, PTH induces a switch in mature IDG-SW3 cells from a osteocyte-like cell to a more motile phenotype. Overall design: RNA expression profiles of control and PTH-treated 28 day differentiated IDG-SW3 cells.
Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms.
No sample metadata fields
View SamplesHSC (Sca+ SP) were isolated from 8-12 week C57B6 mice at various time points after treatment with 5-Fluorouracil. RNA was isolated from 50,000-100,000 FACS sorted cells and subjected to two rounds of T7 based linear amplification using Ambion's Message Amp kit. Two replicates from each time point were analyzed.
Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
No sample metadata fields
View SamplesLoss of function of the tumor suppressor BRCA1 (Breast Cancer 1) protein is responsible for numerous familial and sporadic breast cancers. We previously identified PABP1 as a novel BRCA1 partner and showed that BRCA1 modulates translation through its interaction with PABP1. We showed that the global translation was diminished in BRCA1-depleted cells and increased in BRCA1-overexpressing cells. Our findings raised the question whether BRCA1 affects translation of all cytoplasmic cellular mRNAs or whether it specifically targets a subset of mRNAs.
BRCA1-Dependent Translational Regulation in Breast Cancer Cells.
Cell line
View SamplesTranscriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries
Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.
Sex
View SamplesMedulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options.
Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.
Sex, Age
View SamplesIn this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Overall design: Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.
Specimen part, Treatment, Subject
View SamplesPhenotypes representative of normal, transformed and experimentally manipulated human B cells related to the germinal center structure.
Reverse engineering of regulatory networks in human B cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
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