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| 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
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| 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.
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| 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.
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| 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
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| Organization name |
Cancer Research Center of Lyon
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| Street address |
28 rue Laennec
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| City |
Lyon |
| ZIP/Postal code |
69373 cedex 08 |
| Country |
France |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| 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 |
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| 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 |
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