5-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 have sampled several tumour regions from nine clear cell renal cell carcinoma (ccRCC) patients to investigate intra-tumour heterogeneity.
Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing.
Sex, Age, Specimen part, Subject
View SamplesWe have sampled several tumour regions from a single patient before and after everolimus treatment, including both primary and metastatic site samples to investigate intra-tumour heterogeneity.
No associated publication
Age, Specimen part, Treatment
View SamplesWe have sampled several tumour regions from a single ccRCC patient after 6 weeks everolimus treatment, including both primary and metastatic site samples to investigate intra-tumour heterogeneity.
No associated publication
Age, Specimen part, Disease, Disease stage
View SamplesThere have been few studies that have focused on the periplaque regions surrounding demyelinated plaques, especially in spinal cords. Areas of incomplete demyelination have been demonstrated but poorly studied. The present study aimed to analyze the molecular immunopathology of periplaque demyelinated lesions (PDLs) in the spinal cord of patients with secondary progressive multiple sclerosis (MS).
Tissue remodeling in periplaque regions of multiple sclerosis spinal cord lesions.
Sex, Specimen part
View SamplesBackground: Even though much progress has been made in the understanding of the molecular nature of glioma, the survival rates of patients affected of this tumour have not changed significantly during these years. Thus, a deeper understanding of this malignancy is still needed in order to predict its outcome and improve patient treatment. Here, we report that VAV1, a GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration.
No associated publication
Sex, Age
View SamplesComparison of skin samples (neck skin, non photoexposed) from aged women with various perceived age
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesPilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes.
Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation.
Cell line, Treatment
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