论文部分内容阅读
AIM To determine the role of hepatitis B virus X protein(HBx), HBx in regulating hepatic progenitor cell(HPC)-like features in hepatocellular carcinoma(HCC) and the underlying molecular mechanisms.METHODS We used a retrovirus vector to introduce wild type HBx or empty vector into Hep G2 cells. We then used these cells to analyze cell proliferation, senescence, transformation, and stem-like features. Gene expression profiling was carried out on Affymetrix GeneC hip Human U133A2.0 ver.2 arrays according to the manufacturer’s protocol. Unsupervised hierarchical clustering analysis and Class Comparison analysis were performed by BRB-Array Tools software Version 4.2.2. A total of 238 hepatitis B virus(HBV)-related HCC patients’ array data were used for analyzing clinical features.RESULTS The histone demethylase KDM5 B was significantlyhighly expressed in HBV-related HCC cases(P < 0.01). In HBV proteins, only HBx up-regulated KDM5 B by activating c-myc. Hepatic stem cell(Hp SC) markers(EpC AM, AFP, PROM1, and NANOG) were significantly highly expressed in KDM5B-high HCC cases(P < 0.01). KDM5 B played an important role in maintaining HpS Clike features and was associated with a poor prognosis. Moreover, inhibition of KDM5 B suppressed spheroid formation and cell invasion in vitro.CONCLUSION HBx activates the histone demethylase KDM5 B and induces HPC-like features in HCC. Histone demethylases KDM5 B may be an important therapeutic target against HBV-related HCC cases.
AIM To determine the role of hepatitis B virus X protein(HBx), HBx in regulating hepatic progenitor cell(HPC)-like features in hepatocellular carcinoma(HCC) and the underlying molecular mechanisms.METHODS We used a retrovirus vector to introduce wild type HBx Or empty vector into Hep G2 cells. We then used these cells to analyze cell proliferation, senescence, transformation, and stem-like features. Gene expression profiling was carried out on Affymetrix GeneC hip Human U133A2.0 ver.2 arrays according to the manufacturer’s Protocol. Unsupervised hierarchical clustering analysis and Class Comparison analysis were performed by BRB-Array Tools software Version 4.2.2. A total of 238 hepatitis B virus(HBV)- related HCC patients’ array data were used for analyzing clinical features.RESULTS The histone Demethylase KDM5 B was significantly highly expressed in HBV-related HCC cases (P < 0.01). In HBV proteins, only HBx up-regulated KDM5 B by activating c-myc. Hepatic stem cell (Hp SC) markers (EpC A M, AFP, PROM1, and NANOG) were significantly highly expressed in KDM5B-high HCC cases (P < 0.01). KDM5 B played an important role in maintaining HpS Clike features and was associated with a poor prognosis. Also, inhibition of KDM5 B Suppress spheroid formation and cell invasion in vitro.CONCLUSION HBx activates the histone demethylase KDM5 B and induces HPC-like features in HCC. Histone demethylases KDM5 B may be an important therapeutic target against HBV-related HCC cases.