BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation

Zhu, Lijing; Pan, Yan; Chen, Xiaoying; Hou, Pan‐Fei

doi:10.3892/ol.2020.11445

Cited by 50 publications

(54 citation statements)

References 29 publications

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“…shRNA silencing inhibits the expression of BUB1 gene in glioblastoma tumor cells, thereby reducing the proliferation and tumorigenicity of tumor cells in vivo and in vitro ( Yu et al, 2019 ). Increased BUB1 expression signally facilitates cell proliferation, while decreased BUB1 expression restrains liver cancer cells proliferation ( Zhu et al, 2020 ). The proliferation, migration, and invasion of PCa cell lines can be enhanced via BUB1B overexpression ( Fu et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Analysis of Potential Key Genes Associated With Hepatocellular Carcinoma Based on Integrated Bioinformatics Methods

Lin

Cheng

et al. 2021

Front. Genet.

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BackgroundHepatocellular carcinoma (HCC) is a type of primary liver tumor with poor prognosis and high mortality, and its molecular mechanism remains incompletely understood. This study aimed to use bioinformatics technology to identify differentially expressed genes (DEGs) in HCC pathogenesis, hoping to identify novel biomarkers or potential therapeutic targets for HCC research.MethodsThe bioinformatics analysis of our research mostly involved the following two datasets: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). First, we screened DEGs based on the R packages (limma and edgeR). Using the DAVID database, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were carried out. Next, the protein-protein interaction (PPI) network of the DEGs was built in the STRING database. Then, hub genes were screened through the cytoHubba plug-in, followed by verification using the GEPIA and Oncomine databases. We demonstrated differences in levels of the protein in hub genes using the Human Protein Atlas (HPA) database. Finally, the hub genes prognostic values were analyzed by the GEPIA database. Additionally, using the Comparative Toxicogenomics Database (CTD), we constructed the drug-gene interaction network.ResultsWe ended up with 763 DEGs, including 247 upregulated and 516 downregulated DEGs, that were mainly enriched in the epoxygenase P450 pathway, oxidation-reduction process, and metabolism-related pathways. Through the constructed PPI network, it can be concluded that the P53 signaling pathway and the cell cycle are the most obvious in module analysis. From the PPI, we filtered out eight hub genes, and these genes were significantly upregulated in HCC samples, findings consistent with the expression validation results. Additionally, survival analysis showed that high level gene expression of CDC20, CDK1, MAD2L1, BUB1, BUB1B, CCNB1, and CCNA2 were connected with the poor overall survival of HCC patients. Toxicogenomics analysis showed that only topotecan, oxaliplatin, and azathioprine could reduce the gene expression levels of all seven hub genes.ConclusionThe present study screened out the key genes and pathways that were related to HCC pathogenesis, which could provide new insight for the future molecularly targeted therapy and prognosis evaluation of HCC.

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Section: Discussionmentioning

confidence: 99%

Identification and Analysis of Potential Key Genes Associated With Hepatocellular Carcinoma Based on Integrated Bioinformatics Methods

Lin

Cheng

et al. 2021

Front. Genet.

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“…Incorrect segregation of sister chromatids during mitosis may lead to aneuploidy which is found in many types of tumors [ 1 , 2 ]. The Budding Uninhibited By Benzimidazoles (BUB1, BUB1B, and BUB3) gene family plays a central role in spindle checkpoint during mitosis [ 3 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma

Long

Tian

et al. 2021

Aging

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Budding Uninhibited By Benzimidazoles are a group of genes encoding proteins that play central roles in spindle checkpoint during mitosis. Improper mitosis may lead to aneuploidy which is found in many types of tumors. As a key mediator in mitosis, the dysregulated expression of BUBs has been proven to be highly associated with various malignancies, such as leukemia, gastric cancer, breast cancer, and liver cancer. However, bioinformatic analysis has not been applied to explore the role of the BUBs in sarcomas. Herein, we investigate the transcriptional and survival data of BUBs in patients with sarcomas using Oncomine, Gene Expression Profiling Interactive Analysis, Cancer Cell Line Encyclopedia, Kaplan-Meier Plotter, LinkedOmics, and the Database for Annotation, Visualization and Integrated Discovery. We found that the expression levels of BUB1, BUB1B and BUB3 were higher in sarcoma samples and cell lines than in normal controls. Survival analysis revealed that the higher expression levels of BUB1, BUB1B and BUB3 were associated with lower overall and disease-free survival in patients with sarcomas. This study implies that BUB1, BUB1B and BUB3 are potential treatment targets for patients with sarcomas and are new biomarkers for the prognosis of sarcomas.

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“…Mug1 serves as an inhibitor of proteolytic enzyme that prevents the degradation of cartilage extracellular matrix [56]. In addition, Cdc25b, Mki67, Bub1, Ccne2, Mphosph8, G2e3, Dyrk3 and Cep70 are considered to be essential genes involved in cell proliferation [57][58][59][60][61][62][63]. Thus, these results suggest that DAE play a potential role in regulating articular cartilage formation, growth and repair by controling multiple functional genes involved in chondrocyte commitment, survival, proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 92%

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

Yao¹,

Zhou²,

Zhang³

et al. 2020

Preprint

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Background Deer antler is considered as a precious traditional Chinese medicinal material, and has been widely used to reinforce kidney’s yang, nourish essence and strengthen bone function. The most prominent bioactive components in deer antler are water-soluble proteins that play potential roles in bone formation and repair. The aim of this study was to explore the molecular control and therapeutic targets of deer antler extract (DAE) on articular cartilage. Methods DAE was prepared as previously described. All rats were randomly divided into Blank group and DAE group (10 rats per group) after 7-day adaptive feeding. The rats in DAE group were orally administrated with DAE at a dose of 0.2 g/kg per day for 3 weeks and the rats in Blank group were fed with drinking water. Total RNA was isolated from the articular cartilage of knee joints. RNA sequencing (RNA-seq) experiment combined with quantitative real-time polymerase chain reaction (qRT-PCR) verification assay were carried out to explore the molecular control and therapeutic targets of DAE on articular cartilage. Results We demonstrated that DAE played a potential role in promoting cartilage formation, growth and repair, and inhibiting cartilage degeneration and inflammation. These effects were possibly achieved by accelerating the expression of functional genes involved in chondrocyte commitment, survival, proliferation and differentiation, and suppressing the expression of susceptibility genes involved in the pathophysiology of osteoarthritis. Conclusions DAE might serve as a chondroprotective agent for treating cartilage degeneration and inflammation by boosting the ability of cartilage growth and repair. Thus, our findings will contribute towards deepening the knowledge about the molecular control and therapeutic targets of DAE on the treatment of osteoarthritis.

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BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation

Cited by 50 publications

References 29 publications

Identification and Analysis of Potential Key Genes Associated With Hepatocellular Carcinoma Based on Integrated Bioinformatics Methods

Identification and Analysis of Potential Key Genes Associated With Hepatocellular Carcinoma Based on Integrated Bioinformatics Methods

Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

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