|
|
GEO help: Mouse over screen elements for information. |
|
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 |
GSM2045603 |
Polysomal fraction of 5FU-treated HCT116 cells, biological rep3 |
GSM2045604 |
Non-Polysomal fraction of 5FU-untreated HCT116 cells, biological rep2 |
GSM2045605 |
Non-Polysomal fraction of 5FU-untreated HCT116 cells, biological rep3 |
GSM2045606 |
Polysomal fraction of 5FU-untreated HCT116 cells, biological rep2 |
GSM2045607 |
Polysomal fraction of 5FU-untreated HCT116 cells, biological rep3 |
|
Relations |
BioProject |
PRJNA309671 |
Supplementary file |
Size |
Download |
File type/resource |
GSE77180_RAW.tar |
177.6 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
|
|
|
|
|