DAX-1 Inhibits Hepatocellular Carcinoma Proliferation by Inhibiting β-Catenin Transcriptional Activity
DAX-1 Inhibits Hepatocellular Carcinoma Proliferation by Inhibiting β-Catenin Transcriptional Activity
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DOI：
10.1159/000363038
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Jin, Jun-Zhe
中科院分区：
文献类型：
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作者：
Jiang, Hong-Lei;Xu, Dong;Jin, Jun-Zhe
背景/目的：肝细胞癌（HCC）是最常见的肝癌类型。DAX 1（dose-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome，gene 1）是核受体家族的一个非典型成员，由于缺乏经典的DNA结合结构域而被认为在发育，特别是性别决定和类固醇生成中具有重要作用。先前的研究还表明DAX-1在内分泌和性类固醇依赖性肿瘤如肾上腺皮质、垂体、子宫内膜和卵巢肿瘤中起关键作用。然而，其在HCC发展中的生物学作用在很大程度上仍未被探索。方法：采用Real-time PCR和Western blot检测DAX-1在肝癌组织和肝癌细胞株中的表达。免疫沉淀法（IP）检测DAX-1与β-Catenin的相互作用。小干扰RNA（siRNA）用于沉默DAX-1的表达。用BrdU掺入法和细胞周期分析法检测DAX-1在肝癌细胞增殖中的作用。通过迁移和侵袭实验检测DAX-1在肝癌细胞中的转移能力。结果：在本研究中，我们发现DAX-1的mRNA和蛋白水平在HCC组织和细胞系中下调。此外，DAX-1的过表达可以抑制几种肝癌细胞系的细胞增殖，而其使用小干扰RNA的敲低则促进细胞增殖。在分子水平上，我们证明DAX-1可以与β-连环蛋白相互作用并减弱其转录活性。结论：因此，我们的研究结果表明，以前未知的DAX-1/β-连环蛋白分子网络控制HCC的发展。版权所有（C）2014 S. Karger AG，巴塞尔
Background/Aims: Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored. Methods: Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and beta-Catenin. Small interfering RNA (si RNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells. Results: In the present study, we found that m RNA and protein levels of DAX-1 were down regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with beta-Catenin and attenuate its transcriptional activity. Conclusion: Therefore, our results suggest a previously unknown DAX-1/ beta-Catenin molecular network controlling HCC development. Copyright (C) 2014 S. Karger AG, Basel