Role of the RNA-binding protein HuR in colon carcinogenesis.
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 beta-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.
López de Silanes
Isabel
I
Laboratory of Cellular and Molecular Biology, National Institute of Health, Baltimore, MD 21224, USA.
Fan
Jinshui
J
Yang
Xiaoling
X
Zonderman
Alan B
AB
Potapova
Olga
O
Pizer
Ellen S
ES
Gorospe
Myriam
M
D000818:Animals; D000954:Antigens, Surface; D001483:Base Sequence; D002467:Cell Nucleus / Q000473:pathology / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003593:Cytoplasm / Q000473:pathology / Q000502:physiology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016601:RNA-Binding Proteins