Abstract
Background
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.
Methods
In this study, we employed HCC cells to investigate the role of Pokemon in the invasion of HCC with multidisciplinary approaches.
Results
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.
Conclusion
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.
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Funding
This study was funded by the Jiangsu Provincial Special Program of Medical Science (BL2013021) and the Huai’an Science foundation (SN12037).
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Jing Kong, Xiaoping Liu, Xiangqian Li, Jinsheng Wu, Ning Wu, Jun Chen, and Fang Fang declare that they have no conflict of interest.
Ethical standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Huai’an First People’s Hospital, China) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. Fresh HCC samples were collected from patients with their written informed consent at the Department of Hepatopancreatobiliary Surgery, Huai’an First People’s Hospital (Huai’an, China). This study had been approved by the Ethical Review Board in the Review Board of Huai’an First People’s Hospital (No. 201403, Huai’an, China).
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Kong, J., Liu, X., Li, X. et al. Pokemon promotes the invasiveness of hepatocellular carcinoma by enhancing MEF2D transcription. Hepatol Int 10, 493–500 (2016). https://doi.org/10.1007/s12072-015-9697-y
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DOI: https://doi.org/10.1007/s12072-015-9697-y