Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase

Cheng, Ping; Li, Yuhua; Yang, Liping; Shi, Wei; Mao, Yong-Qiu; Chen, Ping; Lv, Huimin; Tang, Qingqing; Wei, Yuquan

doi:10.3892/or_00000542

Cited by 29 publications

(2 citation statements)

References 24 publications

(34 reference statements)

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“…Previous studies have shown that CDK1/CCNB1 inhibits the p53 signaling pathway and regulate the development of HCC [ 8 ]. An in vitro study demonstrated that HBV X protein (HBx) induces G2/M phase arrest and apoptosis through continuous activation of CDK1/CCNB1 kinase [ 31 ]. Other studies reported that both CCNB1 and CDK1 are overexpressed in HBV-related HCC tissues and are associated with poor survival [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

Zhang¹,

Feng²,

Wu³

et al. 2021

Pathol. Oncol. Res.

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Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China.Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes’ protein expression levels.Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC.Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

Zhang¹,

Feng²,

Wu³

et al. 2021

Pathol. Oncol. Res.

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“…HIV-1 Vpr facilitated apoptosis by targeting the mitochondrial permeability transition pore, which might benefit the depletion of CD4 + lymphocytes [38]. HBV X protein induced apoptosis through sustained activation of cyclin B1-CDK1 kinase, likely contributing to cell growth inhibition [39].…”

Section: Discussionmentioning

confidence: 99%

Intrinsic apoptosis and cytokine induction regulated in human tonsillar epithelial cells infected with enterovirus A71

et al. 2021

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Enterovirus A71 (EV-A71) has emerged as a clinically important neurotropic virus following poliovirus eradication. Recent studies have shown that human tonsillar epithelial cell lines (UT-SCC-60A and UT-SCC-60B) were susceptible to EV-A71, suggesting that human tonsillar crypt epithelium could be important in EV-A71 pathogenesis. However, the mechanism about how EV-A71 infects the upper oro-digestive tract remains largely unclear. In this study, we demonstrated that the human tonsillar epithelial cells infected with EV-A71 underwent apoptotic, in which cytochrome c was released from the mitochondria to the cytosol and caspase-9 was activated, while caspase-2 and -8 were not cleaved or activated during the infection. A selective inhibitor of caspase-9, Z-LEHD-FMK, inhibited the cleavage of the executioner caspase-3 and -7, indicating that only mitochondria-mediated intrinsic apoptotic pathway was activated in EV-A71-infected tonsillar epithelial cells. No evidence of pyroptosis or necroptosis was involved in the cell death. EV-A71 infection induced interferon, pro-inflammatory cytokines and chemokines, including IFN-β, IL-6, CCL5, and TNF-α in tonsillar epithelial cells, which may play a critical role in EV-A71-caused herpangina. Our data indicated that the induction of the cytokines was partially regulated by the mitogen-activated protein kinases (MAPKs) signaling pathway. The findings unveiled the host response to EV-A71 and its regulation mechanism, and will further our understanding the significance about the tonsillar crypt epithelium as the initial and primary portal in viral pathogenesis for EV-A71 infection.

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Vitamin A-coupled liposomes carrying TLR4-silencing shRNA induce apoptosis of pancreatic stellate cells and resolution of pancreatic fibrosis

et al. 2018

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Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase

Cited by 29 publications

References 24 publications

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

Intrinsic apoptosis and cytokine induction regulated in human tonsillar epithelial cells infected with enterovirus A71

Vitamin A-coupled liposomes carrying TLR4-silencing shRNA induce apoptosis of pancreatic stellate cells and resolution of pancreatic fibrosis

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