Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2019; 11(2): 71-90
Published online Feb 15, 2019. doi: 10.4251/wjgo.v11.i2.71
AU-rich element-binding proteins in colorectal cancer
Noémie Legrand, Dan A Dixon, Cyril Sobolewski
Noémie Legrand, Department of Microbiology, Faculty of Medicine, University of Geneva, Geneva CH-1211, Switzerland
Dan A Dixon, Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, and University of Kansas Cancer Center, Kansas City, KS 66045, United States
Cyril Sobolewski, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva CH-1211, Switzerland
Author contributions: Legrand N wrote the manuscript; Sobolewski C performed the supervision and writing of the manuscript; Dixon DA performed the critical revision of the manuscript for important intellectual content and contributed to the overall writing of the manuscript; All authors critically revised the manuscript and approved its final version.
Supported by the National Institutes of Health/National Cancer Institute Cancer Center Support grant P30 CA168524 (DD); the work of Dr. Cyril Sobolewski is currently supported by a grant of the Geneva Cancer League (Grant no. 1711).
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Cyril Sobolewski, PhD, Research Associate, Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, CMU, 1 rue Michel-Servet, Geneva CH-1211, Switzerland.
Telephone: +41-22-3795421
Received: November 6, 2018
Peer-review started: November 10, 2018
First decision: November 28, 2018
Revised: December 11, 2018
Accepted: January 1, 2019
Article in press: January 1, 2019
Published online: February 15, 2019

Trans-acting factors controlling mRNA fate are critical for the post-transcriptional regulation of inflammation-related genes, as well as for oncogene and tumor suppressor expression in human cancers. Among them, a group of RNA-binding proteins called “Adenylate-Uridylate-rich elements binding proteins” (AUBPs) control mRNA stability or translation through their binding to AU-rich elements enriched in the 3’UTRs of inflammation- and cancer-associated mRNA transcripts. AUBPs play a central role in the recruitment of target mRNAs into small cytoplasmic foci called Processing-bodies and stress granules (also known as P-body/SG). Alterations in the expression and activities of AUBPs and P-body/SG assembly have been observed to occur with colorectal cancer (CRC) progression, indicating the significant role AUBP-dependent post-transcriptional regulation plays in controlling gene expression during CRC tumorigenesis. Accordingly, these alterations contribute to the pathological expression of many early-response genes involved in prostaglandin biosynthesis and inflammation, along with key oncogenic pathways. In this review, we summarize the current role of these proteins in CRC development. CRC remains a major cause of cancer mortality worldwide and, therefore, targeting these AUBPs to restore efficient post-transcriptional regulation of gene expression may represent an appealing therapeutic strategy.

Keywords: Colorectal cancer, Adenylate-Uridylate-rich element-binding proteins, Oncogenes, Tumor suppressors, Post-transcriptional regulation

Core tip: Colorectal cancer (CRC) is a deadly cancer associated with the deregulation of multiple genetic and epigenetic mechanisms, leading to the silencing of tumor suppressors and the induction of both oncogenes and inflammation-related genes. Among them, a novel class of RNA-binding proteins called Adenylate-Uridylate-rich element-binding proteins have been involved in the post-transcriptional regulation of genes linked to CRC tumorigenesis. Current findings indicate the major regulatory roles these RNA-binding proteins have on deregulated pathways associated with CRC. Therefore, targeting these proteins may represent a novel and efficient therapeutic approach.