Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research

XiaoMin Wang²  ZhenYu Yin²  WenXiu Zhao²  YaPing Xu¹  Sheng Zhang²  JianFeng Xu¹  Jie Li¹  Fei He¹ 

[1]Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma (based on Xiamen University), Xiamen, Fujian, China

[2]Department of Hepatobiliary Surgery, Xiamen University Affiliated Zhong Shan Hospital, Xiamen, China

关键词: Metastases;    Invasion;    Migration;    Poor prognosis;    ARID1A;    Hepatocellular carcinoma;   

Others  :  1220701
DOI  :  10.1186/s13046-015-0164-3

 received in 2015-03-13, accepted in 2015-05-06,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2015 He et al.; licensee BioMed Central.

【 图 表 】

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