Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2017

Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism

Anne Vincent
Julie Pannequin
Nathalie Pion
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Alexandre David
Didier Auboeuf
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Martin Dutertre
Virginie Marcel

Résumé

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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Dates et versions

hal-03079241 , version 1 (17-12-2020)

Identifiants

Citer

Zeina Bash-Imam, Gabriel Thérizols, Anne Vincent, Julie Pannequin, Florian Lafôrets, et al.. Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism. Oncotarget, 2017, 8 (28), pp.46219-46233. ⟨10.18632/oncotarget.17597⟩. ⟨hal-03079241⟩
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