Pokemon promotes the invasiveness of hepatocellular carcinoma by enhancing MEF2D transcription

被引:19
|
作者
Kong, Jing [1 ]
Liu, Xiaoping [1 ]
Li, Xiangqian [1 ]
Wu, Jinsheng [2 ]
Wu, Ning [3 ]
Chen, Jun [1 ]
Fang, Fang [1 ]
机构
[1] Huaiyin Inst Technol, Fac Life Sci & Chem Engn, 1 Meicheng Rd East, Huaian 223003, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Hepatopancreatobiliary Surg, 6 Beijing Rd West, Huaian 223300, Jiangsu, Peoples R China
[3] Chinese Acad Sci, Inst Oceanol, 7 Nanhai Rd, Qingdao 266071, Shandong, Peoples R China
关键词
Pokemon; MEF2D; HCC; CANCER CELLS; EXPRESSION; GROWTH;
D O I
10.1007/s12072-015-9697-y
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Pokemon, a master oncogene crucial for the tumorigenicity and progression of a variety of cancers, has been demonstrated to enhance the proliferation and survival of hepatocellular carcinoma (HCC). However, the contribution of Pokemon to the invasiveness of HCC has not yet been studied. In this study, we employed HCC cells to investigate the role of Pokemon in the invasion of HCC with multidisciplinary approaches. Pokemon overexpression was found to be closely associated with invasion and intrahepatic metastasis of HCC in clinical specimens. Suppression of Pokemon attenuated the invasion of HCC cells by in vitro transwell and wound-healing assays. Myocyte enhancer factor 2D (MEF2D), an oncogene that can promote the invasiveness of HCC, was found to be underexpressed during Pokemon silencing in HCC cells. Restoration of MEF2D abolished the effect of Pokemon downregulation on the migration of HCC cells. Further experiments verified that Pokemon binds two putative recognition sites located within the upstream region of the MEF2D promoter and enhances its transcription. The association between Pokemon and MEF2D was further confirmed in HCC specimens. Animal experiments further confirmed that Pokemon downregulation attenuated the metastasis of HCC cells in mice. Collectively, Pokemon was found to enhance the migration and invasion of HCC by increasing MEF2D expression. Thus, targeting Pokemon and MEF2D may be an effective strategy to suppress the metastasis of HCC.
引用
收藏
页码:493 / 500
页数:8
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