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

Oncotarget
Zeina Bash-ImamJean-Jacques Diaz

Abstract

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 syn...Continue Reading

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Citations

Oct 16, 2019·The Journal of Pharmacy and Pharmacology·Zhicong ZengYinzhi Song
May 28, 2020·Cancers·Stefanie SchmidtArmin Wiegering
Nov 22, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jenny EralesJean-Jacques Diaz
Apr 24, 2019·Physical Review Letters·Jérémie MargueritatThomas Dehoux
Sep 30, 2018·Cancer Discovery·Stéphanie GachetJean Soulier
Jan 4, 2022·Critical Reviews in Food Science and Nutrition·Amirhossein SheidaHamed Mirzaei

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Datasets Mentioned

BETA
GSE77180

Methods Mentioned

BETA
immunoprecipitation
PCR
transfection

Software Mentioned

DAVID
GraphPad Prism
GraphPad

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