Abstract
Polycomb gene products play a crucial role in the development of highly malignant phenotypes and aggressive cancer progression in a variety of cancers; however, their role in hepatocellular carcinoma remains unclear. First, we analyzed the impact of EZH2 and BMI1 modulation on cell growth of HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays revealed marked growth inhibition after EZH2 or BMI1 knockdown. In addition, simultaneous knockdown of these 2 genes further augmented cell growth inhibitory effects. Next, we conducted immunohistochemical assessment of 86 hepatocellular carcinoma surgical specimens, evaluating the correlation between EZH2 and BMI1 protein expression and clinicopathologic features. High-level EZH2 and BMI1 expression was detected in 57 (66.3%) and 52 tumor tissues (60.5%), respectively. Among these, 48 tumor tissues (55.8%) showed colocalization of EZH2 and BMI1 in almost all tumor cells. The cumulative recurrence rate, but not survival rate, was significantly higher in patients positive for EZH2 (P = .029) and BMI1 (P = .039) than in their negative counterparts, as determined by Kaplan-Meier analysis. These data indicate that EZH2 and BMI1 may cooperate in initiation and progression of hepatocellular carcinoma.
MeSH terms
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Aged
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Aged, 80 and over
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Carcinoma, Hepatocellular / surgery
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Cell Line, Tumor
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Cell Proliferation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enhancer of Zeste Homolog 2 Protein
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Female
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Fluorescent Antibody Technique, Indirect
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Humans
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Immunohistochemistry
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology
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Liver Neoplasms / surgery
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Male
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Middle Aged
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Polycomb Repressive Complex 1
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Polycomb Repressive Complex 2
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Polycomb-Group Proteins
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Tetrazolium Salts / analysis
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Tetrazolium Salts / metabolism
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Thiazoles / analysis
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Thiazoles / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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BMI1 protein, human
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DNA-Binding Proteins
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Nuclear Proteins
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Polycomb-Group Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Repressor Proteins
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Tetrazolium Salts
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Thiazoles
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Transcription Factors
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3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Polycomb Repressive Complex 1