Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR.
Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR.
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DOI：
10.1093/nar/gkl698
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发表时间：
2006
影响因子：
14.9
通讯作者：
Jeong S
中科院分区：
文献类型：
--
作者：
Lee HK;Jeong S
环氧合酶-2 (COX-2) mRNA在大多数人类结直肠癌中被诱导表达。在人结肠癌细胞中，转录调控在COX-2表达中起着关键作用，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、生长因子等信号调控。β-Catenin是Wnt信号通路中的关键转录因子，可激活COX-2的转录。在NIH3T3和293T细胞中，我们发现通过激活β-catenin， COX-2 mRNA也基本稳定。我们在COX-2 3 ' -非翻译区（3 ' -UTR）的近端区域鉴定了β-catenin响应元件，并在体外和体内发现β-catenin与3 ' -UTR的富au元件（ARE）相互作用。有趣的是，β-catenin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-catenin结合，促进了β-catenin依赖性COX-2 mRNA的稳定。综上所述，我们提供了β-catenin作为rna结合因子和COX-2 mRNA稳定调节因子的证据。
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. β-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 β-catenin in NIH3T3 and 293T cells. We identified the β-catenin-responsive element in the proximal region of the COX-2 3′-untranslated region (3′-UTR) and showed that β-catenin interacted with AU-rich elements (ARE) of 3′-UTR in vitro and in vivo. Interestingly, β-catenin induced the cytoplasmic localization of the RNA stabilizing factor, HuR, which may bind to β-catenin in an RNA-mediated complex and facilitate β-catenin-dependent stabilization of COX-2 mRNA. Taken together, we provided evidences for β-catenin as an RNA-binding factor and a regulator of stabilization of COX-2 mRNA.
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