Posttranscriptional regulation of cancer traits by HuR

Abstract

Cancer-related gene expression programs are strongly influenced by posttranscriptional mechanisms. The RNA-binding protein HuR is highly abundant in many cancers. Numerous HuR-regulated mRNAs encode proteins implicated in carcinogenesis. Here, we review the collections of HuR target mRNAs that encode proteins responsible for implementing five major cancer traits. By interacting with specific mRNA subsets, HuR enhances the levels of proteins that (1) promote cell proliferation, (2) increase cell survival, (3) elevate local angiogenesis, (4) help the cancer cell evade immune recognition, and (5) facilitate cancer cell invasion and metastasis. We propose that HuR exerts a tumorigenic function by enabling these cancer phenotypes. We discuss evidence that links HuR to several specific cancers and suggests its potential usefulness in cancer diagnosis, prognosis, and therapy.

Figure 1. HuR protein and post-translational modification by cancer-related enzymes

The HuR three RNA recognition motifs (RRMs) and hinge region (amino acids 186-244), containing the HuR nucleocytoplasmic shuttling (HNS) domain, are indicated. The specific residues (Amino Acid Positions, first column) implicated in different post-translational modifications (second column) and the cancer-related enzymes that carry out the modifications (third column) are listed. The consequences of modification at each residue are listed under ‘Impact on HuR Function’. n.d., not determined.

Figure 2. HuR-target mRNAs implicated in establishing cancer traits

The subsets of HuR target mRNAs involved in five major cancer-acquired phenotypes are listed. * denotes transcripts whose expression decreases in the presence of HuR, either because HuR represses their translation (c-Myc, p27) or because its association with HuR is reduced in cancer (TSP1).