AU-rich element-binding proteins in colorectal cancer

Abstract

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.

The Fragile X Mental Retardation Protein Regulates RIPK1 and Colorectal Cancer Resistance to Necroptosis

“…5,36 In the specific case of CRC, several RBPs have been shown to be dysregulated and associated with survival rate of cancer patients. 35,37 Of note, IMP1, CELF1, and HUR constitute a new set of regulatory RBPs, playing a role in intestinal homeostasis, adaptation to injury, and participation in malignant transformation. 35 Here we show that FMRP expression is significantly increased in human CRC.…”

SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins

“…5e). Furthermore, this clustering reconfirmed that while TIA1 overall prefers uridine-rich sequences [52][53][54], it also interacts with an AU-riched sequences [55], 5 -AAUAAA-3 , which resembles the canonical cleavage and polyadenylation site motif, in event types IAP and TAP in addition to two other significant motifs (Additional file 1: Fig. S33).…”

mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer

“…Many transcripts of these genes contain cis-regulatory sequences in their 3’-UTRs, which can be targeted by AUBPs for post-transcriptional regulation. As for genetic mutations, mRNA stabilization and promotion of the translation of oncogenes or, on the contrary, degradation of tumor-suppressive transcripts may steer cells into abnormal proliferation, inhibition of cell death, increased migration, and metabolic switch characterizing cancer cells [ 124 ]. It is therefore likely that alterations of the expression, activity, or intracellular localization of AUBPs represent key drivers of hepatic carcinogenesis.…”