Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma.
Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma.
复制标题
DOI：
10.1186/s13046-015-0164-3
复制
发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
He F;Li J;Xu J;Zhang S;Xu Y;Zhao W;Yin Z;Wang X
肝细胞癌是世界范围内常见的恶性肿瘤，在亚洲尤为常见。阐明肝细胞癌的分子基础对于开发有针对性的诊断工具和新的治疗方法至关重要。最近的研究发现，富含AT的相互作用结构域包含蛋白1A(ARID1A)是一种广谱的肿瘤抑制因子。我们评估了ARID1A在肝细胞癌中表达降低的临床意义，并探讨了ARID1A介导的肿瘤抑制机制。采用定量聚合酶链式反应、免疫印迹、免疫组织化学方法检测配对的肝癌及癌旁组织中ARID1AmRNA和蛋白的表达。在体外评价ARID1A在MHCC-97H和HuH7肝癌细胞系中的功能，并在体内评价其在肝癌移植瘤模型中的作用。肝细胞癌组织中ARID1AmRNA和蛋白的表达均显著降低，且表达降低与肿瘤的整体转移(包括局部淋巴结转移和远处转移)及预后不良密切相关。在体外，ARID1A基因敲除可促进肝癌细胞的迁移和侵袭，而ARID1A过表达则抑制细胞的迁移和侵袭。E-钙粘附素水平与ARID1A的表达密切相关，提示其在肿瘤的迁移和侵袭中起一定作用。此外，ARID1A和E-钙粘蛋白(CDH1)在肝细胞癌样本中的表达被发现是以协调的方式调节的。此外，ARID1A基因敲除显著增加了体内肝癌肿瘤的生长和肺转移。ARID1A是一种重要的肿瘤抑制因子。在小鼠和人类中，ARID1A的表达降低与肿瘤的进展、转移和总生存期的减少有关。ARID1A可能是一种有希望的肝癌候选治疗靶点。本文的在线版本(doi：10.1186/s13046-015-0164-3)包含补充材料，可供授权用户使用。
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, which is especially prevalent in Asia. Elucidating the molecular basis of HCC is crucial to develop targeted diagnostic tools and novel therapies. Recent studies have identified AT-rich interactive domain-containing protein 1A (ARID1A) as a broad-spectrum tumor suppressor. We evaluated the clinical implications of decreased ARID1A expression in HCC, and investigated the mechanisms of ARID1A-mediated tumor suppression. Quantitative PCR, western blotting, immunohistochemical analysis of ARID1A mRNA and protein expression was conducted in 64 paired HCC and adjacent non-tumorous tissues. ARID1A function was evaluated in vitro in MHCC-97H and Huh7 HCC cell lines, and in vivo in a xenografted HCC tumor model. ARID1A mRNA and protein expression were significantly decreased in HCC tissues, and decreased expression was significantly associated with overall metastasis, including local lymph node and distant metastasis, and poor prognosis. ARID1A knockdown promoted HCC cell migration and invasion in vitro, whereas overexpression of ARID1A inhibited migration and invasion. E-cadherin levels were closely correlated with ARID1A expression, suggesting a role in migration and invasion. In addition, ARID1A and E-cadherin (CDH1) expression were found to be regulated in a coordinated fashion in HCC samples. Furthermore, ARID1A knockdown significantly increased HCC tumor growth and lung metastasis in vivo. ARID1A served as an important tumor suppressor. Decreased expression of ARID1A was associated with tumor progression, metastasis, and reduced overall survival in mice and humans. ARID1A could represent a promising candidate therapeutic target for HCC. The online version of this article (doi:10.1186/s13046-015-0164-3) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.4
作者：
Fernandez-Banet, Julio;Lee, Nikki P.;Kan, Zhengyan
通讯作者：
Kan, Zhengyan
影响因子：
30.8
作者：
Dulak, Austin M.;Stojanov, Petar;Peng, Shouyong;Lawrence, Michael S.;Fox, Cameron;Stewart, Chip;Bandla, Santhoshi;Imamura, Yu;Schumacher, Steven E.;Shefler, Erica;McKenna, Aaron;Carter, Scott L.;Cibulskis, Kristian;Sivachenko, Andrey;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Auclair, Daniel;Thompson, Kristin;Sougnez, Carrie;Onofrio, Robert C.;Guiducci, Candace;Beroukhim, Rameen;Zhou, Zhongren;Lin, Lin;Lin, Jules;Reddy, Rishindra;Chang, Andrew;Landrenau, Rodney;Pennathur, Arjun;Ogino, Shuji;Luketich, James D.;Golub, Todd R.;Gabriel, Stacey B.;Lander, Eric S.;Beer, David G.;Godfrey, Tony E.;Getz, Gad;Bass, Adam J.
通讯作者：
Bass, Adam J.
影响因子：
28.2
作者：
Popovic R;Licht JD
通讯作者：
Licht JD
影响因子：
7.3
作者：
Wiegand, Kimberly C.;Lee, Anna F.;Huntsman, David G.
通讯作者：
Huntsman, David G.
影响因子：
30.8
作者：
Wang, Kai;Kan, Junsuo;Leung, Suet Yi
通讯作者：
Leung, Suet Yi