title: Methylation of nucleolar and coiled-body phosphoprotein 1 is associated with the mechanism of tumorigenesis in hepatocellular carcinoma.
abstract: Nucleolar and coiled-body phosphoprotein 1 (NOLC1) plays an essential role in the synthesis of rRNA and the biosynthesis of ribosomes. Previous studies suggest that NOLC1 is crucial for normal cell growth, and plays a role in the regulation of tumorigenesis of nasopharyngeal carcinoma (NPC) and demonstrate that both NOLC1 and tumor protein 53 work synergistically to activate the MDM2 promoter in NPC cells. Yet, the functioning of NOLC1 in liver cancer remains unknown. The aim of the present study was to understand how the NOLC1 gene is regulated in liver carcinogenesis. In this study, we showed that NOLC1 was silenced or downregulated in liver tumor tissues when compared with that in the matched non-cancer tissues. In addition, human hepatoma cells weakly expressed NOLC1, whereas cultured human normal liver cell lines expressed abundant levels. The hypermethylation status in the promoter CpG1 start region appeared to be correlated with the NOLC1 expression levels in liver cell lines or liver normal and tissue specimens. We found that four CpG dinucleotides were located at the CpG1 start region. Further molecular analysis of mutagenesis indicated that the four CpG dinucleotides play a role in the promoter activity of the NOLC1 gene. The expression of NOLC1 and DNA methylation of its promoter affected cell proliferation and apoptosis. The expression of NOLC1 in hepatoma cell lines was restored following exposure to the demethylation agent, 5-azacytidine. Low expression of NOLC1 in hepatoma cell lines and liver cancer tissues was associated with cyclin D3. In conclusion, our study demonstrated that DNA methylation is a key mechanism of silenced NOLC1 expression in human hepatocellular carcinoma cells, and NOLC1 gene hypermethylation of the four CpG dinucleotides is a potential biomarker for hepatocellular carcinoma.
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
authors: Xuefei
authors: X
authors: Duan
authors: Jinqian
authors: J
authors: Zhang
authors: Shunai
authors: S
authors: Liu
authors: Mengran
authors: M
authors: Zhang
authors: Qi
authors: Q
authors: Wang
authors: Jun
authors: J
authors: Cheng
mesh_terms: D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; C075564:NOLC1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins