CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 May Be Potential Therapeutic Targets for Hepatocellular Carcinoma Using Integrated Bioinformatic Analysis

Yang, Wan-Xia; Pan, Yunyan; You, Chongge

doi:10.1155/2019/1245072

Cited by 77 publications

(67 citation statements)

References 39 publications

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“…Inhibition of CDC20 expression in HCC reduced cell proliferation and induced G2/M cell cycle arrest, showing a positive correlation with TNM staging [ 30 ]. Consistent with our research findings, increased expression of BUB1B is associated with poor prognosis in HCC patients [ 31 ]. KIF11 is highly expressed in blast crisis chronic myelogenous leukemia [ 32 ] and pancreatic cancer [ 33 ].…”

Section: Discussionsupporting

confidence: 92%

Screening and Functional Prediction of Key Candidate Genes in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Chen

Ling

et al. 2020

BioMed Research International

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Background. The molecular mechanism by which hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) is still unknown. The genomic expression profile and bioinformatics methods were used to investigate the potential pathogenesis and therapeutic targets for HBV-associated HCC (HBV-HCC). Methods. The microarray dataset GSE55092 was downloaded from the Gene Expression Omnibus (GEO) database. The data was analyzed by the bioinformatics software to find differentially expressed genes (DEGs). Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, ingenuity pathway analysis (IPA), and protein-protein interaction (PPI) network analysis were then performed on DEGs. The hub genes were identified using Centiscape2.2 and Molecular Complex Detection (MCODE) in the Cytoscape software (Cytoscape_v3.7.2). The survival data of these hub genes was downloaded from the Gene Expression Profiling Interactive Analysis (GEPIA). Results. A total of 2264 mRNA transcripts were differentially expressed, including 764 upregulated and 1500 downregulated in tumor tissues. GO analysis revealed that these DEGs were related to the small-molecule metabolic process, xenobiotic metabolic process, and cellular nitrogen compound metabolic process. KEGG pathway analysis revealed that metabolic pathways, complement and coagulation cascades, and chemical carcinogenesis were involved. Diseases and biofunctions showed that DEGs were mainly associated with the following diseases or biological function abnormalities: cancer, organismal injury and abnormalities, gastrointestinal disease, and hepatic system disease. The top 10 upstream regulators were predicted to be activated or inhibited by Z-score and identified 25 networks. The 10 genes with the highest degree of connectivity were defined as the hub genes. Cox regression revealed that all the 10 genes (CDC20, BUB1B, KIF11, TTK, EZH2, ZWINT, NDC80, TPX2, MELK, and KIF20A) were related to the overall survival. Conclusion. Our study provided a registry of genes that play important roles in regulating the development of HBV-HCC, assisting us in understanding the molecular mechanisms that underlie the carcinogenesis and progression of HCC.

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Section: Discussionsupporting

confidence: 92%

Screening and Functional Prediction of Key Candidate Genes in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Chen

Ling

et al. 2020

BioMed Research International

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“…MCM2 was considered as a potential therapeutic target for cancer treatment, and the level of MCM2 could predict poor prognosis for osteosarcoma [ 21 ], gastric cancer [ 22 ], lung adenocarcinoma [ 23 ], diffuse large B cell lymphoma [ 24 ], and esophageal cancer [ 25 ]. Recent research suggested that MCM2 might be a potential therapeutic target for HCC [ 26 ]. Furthermore, Deng et al found that MCM2 inhibition could increase the sensitivity of carboplatin in ovarian cancer cell [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of the DNA Replication Regulator MCM Complex Expression and Prognostic Significance in Hepatic Carcinoma

Cao

Wang

et al. 2020

BioMed Research International

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Background. The microliposome maintenance (MCM) complex, MCM2-7, is revealed to be involved in multiple cellular processes and plays a key role in the development and progression of human cancers. However, the MCM complex remains poorly elaborated in hepatic carcinoma (HCC). Methods. In the study, we found the mRNA and protein level by bioinformatics. We also explored the prognostic value, genetic alteration, interaction network, and functional enrichment of MCM2-7. The MCM expression and correlation among these MCMs in HCC cell lines were identified by western blot. Results. MCM2-7 was significantly increased in HCC tissues compared to normal liver tissues. The high level of MCM2-7 had a positive correlation with poor prognosis. However, MCM2-7 alterations were not correlated with poor OS. MCMs were both increased in HCC cell lines compared to the normal hepatocyte cell line. Furthermore, the positive correlation was found among MCMs in HCC cell lines. Conclusions. The MCM complex was increased in HCC tissues and cell lines and negatively correlated with prognosis, which might be important biomarkers for HCC.

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“…In the present study, EZH2 also displayed higher expression in tumor tissues compared with adjacent tissues; however, the overall survival assay showed no difference between positive and negative-EZH2. A bioinformatic study on HCC disclosed overexpression of The cell-division cycle protein 20 (CDC20), MAD2L1, and DNA replication licensing factor (MCM3) could predict poor prognosis [32,33]. In our study, partially due to limited clinical samples, CDC20 and MCM3 showed no difference in overall survival analysis.…”

Section: Discussionmentioning

confidence: 55%

Prognostic and Predictive Values of MAD2L1 in Cholangiocarcinoma

Gao¹,

Ouyang²,

Luo³

et al. 2020

Preprint

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Background: This study aimed to investigate the expression of Mitotic arrest deficient 2-like protein 1 (MAD2L1) in cholangiocarcinoma (CCA) and its biological function. Methods: Our study performed bioinformatics to analyze the microarray data from the Gene Expression Omnibus (GEO) database and obtained the differentially expressed genes (DEGs). Enrichment assay and protein-protein interaction networks analysis were conducted to extract hub genes. Mitotic arrest deficient 2-like protein 1 (MAD2L1) was investigated in tumor and adjacent nonneoplastic biliary ducts in 42 samples by immunohistochemistry. Subsequently, MAD2L1 was manipulated, and its function was examined in CCA cell lines and in vivo model. Results: 297 DEGs were extracted from the microarray data. And seven hub genes were defined through the enrichment assay and protein-protein interaction networks analysis. MAD2L1 was picked up as a novel biomarker, according to hierarchical cluster analysis and Kaplan-Meier survival analysis. MAD2L1 was specifically expressed in cancer tissues but not in the surrounding normal tissue, and 31 (73.81%) of 42 CCAs were MAD2L1 positive by immunohistochemistry. MAD2L1 expression was significantly correlated with tumor size, pathological grade, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between MAD2L1 expression and overall survival. Real-time polymerase chain reaction (RT-PCR) and Immunoblotting results further confirmed the results of immunohistochemistry and bioinformatic analysis from the database. In vitro and in vivo models, decreasing MAD2L1 could significantly suppress tumor growth.Conclusion: High MAD2L1 expression predicts the advanced stage of CCA. Targeting MAD2L1 may be a potential tumor suppressor and may provide the biological basis for a new therapeutic strategy.Trial registration: [2020]KY157-01. Registered 1st April 2020 - Retrospectively registered, http://114.255.48.20/login#.

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CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 May Be Potential Therapeutic Targets for Hepatocellular Carcinoma Using Integrated Bioinformatic Analysis

Cited by 77 publications

References 39 publications

Screening and Functional Prediction of Key Candidate Genes in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Screening and Functional Prediction of Key Candidate Genes in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Identification of the DNA Replication Regulator MCM Complex Expression and Prognostic Significance in Hepatic Carcinoma

Prognostic and Predictive Values of MAD2L1 in Cholangiocarcinoma

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