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Series GSE77180 Query DataSets for GSE77180
Status Public on May 23, 2017
Title Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Overall design 8 total samples were analyzed. We generated the following pairwise comparisons: -5FU polysome vs -5FU non-polysome +5FU polysome vs +5FU non-polysome +5FU polysome vs -5FU polysome. Genes and exons with an fold change >= 1.5 and a p-value <= 0.05 were selected.
 
Contributor(s) BASH-IMAM Z, THERIZOLS G, POLAY ESPINOZA M, TEXTORIS J, AUBOEUF D, DUTERTRE M, MARCEL V, DIAZ J
Citation(s) 28515355
Submission date Jan 25, 2016
Last update date Feb 18, 2019
Contact name Virginie MARCEL
E-mail(s) virginie.marcel@lyon.unicancer.fr
Organization name Cancer Research Center of Lyon
Street address 28 rue Laennec
City Lyon
ZIP/Postal code 69373 cedex 08
Country France
 
Platforms (1)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
Samples (8)
GSM2045600 Non-polysomal fraction of 5FU-treated HCT116 cells, biological rep2
GSM2045601 Non-Polysomal fraction of 5FU-treated HCT116 cells, biological rep3
GSM2045602 Polysomal fraction of 5FU-treated HCT116 cells, biological rep2
Relations
BioProject PRJNA309671

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Supplementary file Size Download File type/resource
GSE77180_RAW.tar 177.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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