Journal Article

Role of the RNA-binding protein HuR in human renal cell carcinoma

Sabrina Danilin, Carole Sourbier, Lionel Thomas, Véronique Lindner, Sylvie Rothhut, Valérian Dormoy, Jean-Jacques Helwig, Didier Jacqmin, Hervé Lang and Thierry Massfelder

in Carcinogenesis

Volume 31, issue 6, pages 1018-1026
Published in print June 2010 | ISSN: 0143-3334
Published online March 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq052
Role of the RNA-binding protein HuR in human renal cell carcinoma

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Human conventional renal cell carcinoma (CRCC) remains resistant to therapy. The RNA-binding protein HuR regulates the stability and/or translation of multiple messenger RNAs involved in malignant transformation. In this study, we aimed to evaluate the potential role of HuR in this pathology. Using seven human CRCC cell lines expressing or not the von Hippel-Lindau (VHL) tumor suppressor gene as well as 15 normal/renal cell carcinoma tumor pairs, we showed that HuR is overexpressed in all tumors independently of the VHL status. Futhermore, HuR cytoplasmic presence appears to be more common in early tumor stages, suggesting a role in tumor promotion. We then assessed the effect of HuR knockdown using small interfering RNA in cultured cell and in tumor-bearing mice. Both in vitro and in vivo, we observed that cell growth was inhibited by 60% and that this effect was obtained through an inhibition of cell proliferation and an induction of cell apoptosis. Finally, we found that expression of vascular endothelium growth factor, tumor growth factor-β and of the hypoxia-induced transcription factor-2α as well as the constitutive activation of the oncogenic phosphoinositide 3-kinase/Akt, nuclear factor-kappaB and mitogen-activated protein kinase pathways were decreased in HuR-depleted cells and tumors. All these results suggest a pivotal role for HuR in human CRCC.

Journal Article.  6733 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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