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Role of the RNA-binding protein HuR in colon carcinogenesis

Abstract

Immunohistochemical analysis of paired tumor and normal tissue specimens revealed that the expression and cytoplasmic abundance of the RNA-binding protein HuR increased with malignancy, particularly in colon carcinomas. Interventions to modulate HuR expression in human RKO colon cancer cells altered gene expression profiles and identified β-catenin mRNA as a novel HuR target. Subcutaneous injection of HuR-overexpressing RKO cells into nude mice produced significantly larger tumors than those arising from control populations; conversely, RKO cells expressing reduced HuR through small interference RNA- or antisense HuR-based approaches developed significantly more slowly. We propose that HuR-regulated target mRNA expression contributes to colon cancer growth. Our results suggest a pivotal function for HuR in colon carcinogenesis.

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Abbreviations

CR:

coding region

ELAV:

embryonic lethal abnormal vision

REMSA:

RNA electrophoretic mobility-shift assay

UTR:

untranslated region

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Acknowledgements

We thank MB Kastan for the RKO cells, S Galbán, M Jr Ware, J Robinson, C Galbán, and J Alsruhe for assistance with experimental procedures, and KG Becker and C Cheadle for providing cDNA arrays and guidance in their analysis. We are grateful to our colleagues PJ Morin and DL Longo for critical reading of the manuscript.

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Correspondence to Myriam Gorospe.

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de Silanes, I., Fan, J., Yang, X. et al. Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 22, 7146–7154 (2003). https://doi.org/10.1038/sj.onc.1206862

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