title: Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy.
authors.affiliation: Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Chang Chun, 130031, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Chang Chun, 130031, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Hong
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Chang Chun, 130031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, China-Japan Union Hospital of Jilin University, Chang Chun, 130031, China. chengyanhecc@126.com.
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D064326:MEF2 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; D014157:Transcription Factors; C485514:ZBTB7A protein, human
keywords: Hepatocellular carcinoma; Invasion; MEF2D; Pokemon