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Posttranscriptional regulation of cancer traits by HuR

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Kotb Abdelmohsen, Myriam Gorospe

Published Online: May 06 2010

DOI: 10.1002/wrna.4

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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. Copyright © 2010 John Wiley & Sons, Ltd.

Figure 1.

HuR protein and posttranslational modification by cancer-related enzymes. The HuR three RNA recognition motifs (RRMs) and hinge region (amino acids 186244), containing the HuR nucleocytoplasmic shuttling (HNS) domain, are indicated. The specific residues (amino acid position, first column) implicated in different posttranslational 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.

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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. The symbol * 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 [thrombospondin (TSP1)].

[ Normal View 33K | Magnified View 58K ]

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158 Denkert C, Koch I, von Keyserlingk N, Noske A, Niesporek S, et al. Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2 Mod Pathol 2006 19:1261-1269
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160 Yi X, Zhou Y, Zheng W, Chambers SK. HuR expression in the nucleus correlates with high histological grade and poor disease-free survival in ovarian cancer Aust N Z J Obstet Gynaecol 2009 49:93-98
161 Niesporek S, Kristiansen G, Thoma A, Weichert W, Noske A, et al. Expression of the ELAV-like protein HuR in human prostate carcinoma is an indicator of disease relapse and linked to COX-2 expression Int J Oncol 2008 32:341-347
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David H Bechhofer

Professor David H Bechhofer joined Mount Sinai in 1986, after receiving his PhD from Columbia University in 1984 and doing postdoctoral work at the Public Health Research Institute of New York (moved since to UMDNJ in Newark, NJ). He is now Professor of Medical Education, and Professor of Pharmacology and Systems Therapeutics. His laboratory has been funded by the NIH since 1987, and he has served several times on the NIH Microbial Genetics Study Section as an ad hoc reviewer.

Professor Bechhofer’s current research interests focus on Prokaryotic mRNA decay and stable RNA processing. In particular he and his team study the mechanism of mRNA decay in the Gram-positive bacterium Bacillus subtilis. In early studies, the group showed that the 5’ end of a message is important in determining mRNA half-life, and they are now investigating the specific sites on an mRNA where decay begins.

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Article Title	Posttranscriptional regulation of cancer traits by HuR
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Posttranscriptional regulation of cancer traits by HuR

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