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β-连环蛋白通过与3'-非翻译区富含AU的元件相互作用来稳定环氧化酶-2信使核糖核酸。

Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR.

作者信息

Lee Hee Kyu, Jeong Sunjoo

机构信息

Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.

出版信息

Nucleic Acids Res. 2006;34(19):5705-14. doi: 10.1093/nar/gkl698. Epub 2006 Oct 12.

DOI:10.1093/nar/gkl698
PMID:17040897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1636482/
Abstract

Cyclooxygenase-2 (COX-2) mRNA is induced in the majority of human colorectal carcinomas. Transcriptional regulation plays a key role in COX-2 expression in human colon carcinoma cells, but post-transcriptional regulation of its mRNA is also critical for tumorigenesis. Expression of COX-2 mRNA is regulated by various cytokines, growth factors and other signals. beta-Catenin, a key transcription factor in the Wnt signal pathway, activates transcription of COX-2. Here we found that COX-2 mRNA was also substantially stabilized by activating beta-catenin in NIH3T3 and 293T cells. We identified the beta-catenin-responsive element in the proximal region of the COX-2 3'-untranslated region (3'-UTR) and showed that beta-catenin interacted with AU-rich elements (ARE) of 3'-UTR in vitro and in vivo. Interestingly, beta-catenin induced the cytoplasmic localization of the RNA stabilizing factor, HuR, which may bind to beta-catenin in an RNA-mediated complex and facilitate beta-catenin-dependent stabilization of COX-2 mRNA. Taken together, we provided evidences for beta-catenin as an RNA-binding factor and a regulator of stabilization of COX-2 mRNA.

摘要

环氧化酶-2（COX-2）信使核糖核酸（mRNA）在大多数人类结肠直肠癌中被诱导表达。转录调控在人结肠癌细胞中COX-2的表达中起关键作用，但其mRNA的转录后调控对肿瘤发生也至关重要。COX-2 mRNA的表达受多种细胞因子、生长因子和其他信号调控。β-连环蛋白是Wnt信号通路中的关键转录因子，可激活COX-2的转录。在此，我们发现通过在NIH3T3和293T细胞中激活β-连环蛋白，COX-2 mRNA也能得到显著稳定。我们在COX-2 3'-非翻译区（3'-UTR）近端区域鉴定出β-连环蛋白反应元件，并表明β-连环蛋白在体外和体内均与3'-UTR的富含AU元件（ARE）相互作用。有趣的是，β-连环蛋白诱导了RNA稳定因子HuR的细胞质定位，HuR可能在RNA介导的复合物中与β-连环蛋白结合，并促进β-连环蛋白依赖的COX-2 mRNA稳定。综上所述，我们提供了证据表明β-连环蛋白是一种RNA结合因子以及COX-2 mRNA稳定性的调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/896e00dd10f9/gkl698f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/5320ca0d2c61/gkl698f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/0b7a2d40543f/gkl698f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/937d7e48278e/gkl698f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/896e00dd10f9/gkl698f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/5320ca0d2c61/gkl698f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/7788bc170a37/gkl698f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/1683f1baddf7/gkl698f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/0b7a2d40543f/gkl698f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/937d7e48278e/gkl698f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76ea/1636482/896e00dd10f9/gkl698f6.jpg

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