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Year : 2018  |  Volume : 131  |  Issue : 23  |  Page : 2827-2835

Effect of Upregulated DNA Replication and Sister Chromatid Cohesion 1 Expression on Proliferation and Prognosis in Hepatocellular Carcinoma

1 Chinese Center for Disease Control and Prevention, Beijing 102206, China
2 Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing 100044, China
3 Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China

Correspondence Address:
Prof. Yu Wang
Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0366-6999.246076

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Background: DNA replication and sister chromatid cohesion 1 (DSCC1) (also called DCC1) is a component of an alternative replication factor C complex that loads proliferating cell nuclear antigen onto DNA during S phase of the cell cycle. It is located at 8q24 and frequently amplified in hepatocellular carcinoma (HCC). However, the role of DSCC1 in the carcinogenesis and progress of HCC has not been fully investigated. Here, we aimed to assert the importance of DSCC1 in the HCC. Methods: In this study, copy number variation data and RNA sequencing data were used to calculate the DNA copy number and mRNA expression of DSCC1 in HCC. Quantitative polymerase chain reaction, Western blotting, and immunohistochemistry analysis were used to determine the mRNA and protein level of DSCC1 in HCC. The Kaplan–Meier analysis and univariate and multivariate Cox regression analysis were used to assess the association of DSCC1 with the overall survival (OS) of HCC patients. Moreover, lentiviral shRNA was used to knockdown DSCC1, and then, colony-forming assay, cell cycle assay, and cell proliferation assay were performed to evaluate the impact of DSCC1 silencing on HCC cell lines. Results: We found that DSCC1 was amplified and highly expressed in HCC tumor tissues than in nontumor tissues. We then found that the overexpression of both mRNA and protein of DSCC1 was linked to the bad prognosis of HCC patients. Astonishingly, the protein level of DSCC1 was an independent prognostic factor for OS (hazard ratio, 1.79; 95% confidence interval, 1.17–2.74; P = 0.007). Furthermore, the clonogenic capacity of DSCC1-amplified HCC cell lines (MHCC-97H, MHCC-97L, and Hep3B) was significantly inhibited by transduction of a lentiviral shRNA that targets DSCC1. We also showed that knockdown of DSCC1 induced G0–G1 cell cycle arrest (increased from 60% to more than 80%) and greatly inhibited the proliferation of HCC cell lines. Conclusion: These results suggest that DSCC1 is a putative HCC driver gene that promotes proliferation and is associated with poor prognosis in HCC.


 Abstract in Chinese




方法:利用HCC患者的DNA拷贝数变异数据(CNV)和转录组测序数据(RNA-Seq),分析DSCC1的拷贝数变异和mRNA转录水平;使用荧光定量PCR和Western Blot分析该基因mRNA和编码蛋白的表达水平。进一步使用慢病毒shRNA敲减DSCC1进行功能学验证,分析敲减DSCC1对HCC细胞系增殖和克隆形成能力的影响。


结论: DSCC1是一个潜在的原发性肝细胞癌驱动基因,其过表达能促进增殖并与HCC患者的不良预后相关。

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