Role of the RNA-binding protein HuR in colon carcinogenesis
Role of the RNA-binding protein HuR in colon carcinogenesis
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DOI：
10.1038/sj.onc.1206862
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发表时间：
2003-10-16
期刊：
影响因子：
8
通讯作者：
Gorospe, M
中科院分区：
文献类型：
--
作者：
de Silanes, IL;Fan, JS;Gorospe, M
配对的肿瘤和正常组织标本的免疫组化分析显示，RNA结合蛋白HuR的表达和细胞质丰度随着恶性程度的增加而增加，特别是在结肠癌中。在人RKO结肠癌细胞中调节HuR表达的干预改变了基因表达谱，并将β-连环蛋白mRNA鉴定为新的HuR靶点。皮下注射HuR过表达的RKO细胞到裸鼠中产生的肿瘤比对照人群产生的肿瘤明显更大;相反，通过小干扰RNA或反义HuR为基础的方法表达减少HuR的RKO细胞发育明显更慢。我们认为HuR调节的靶mRNA表达有助于结肠癌的生长。我们的研究结果表明HuR在结肠癌发生中起关键作用。
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 signfiicantly 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.