The role of ubiquitination and deubiquitination in cancer metabolism

Sun, Tianshui; Liu, Zhuonan; Yang, Qing

doi:10.1186/s12943-020-01262-x

Cited by 277 publications

(210 citation statements)

References 306 publications

(354 reference statements)

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“…Other signaling pathways enriched in our analysis may also play role in cancer polyploidy. Accordingly, the protein ubiquitination pathway which is highlighted in our study has previously shown to be involved in DNA damage repair, tumor proliferation, hypoxia adaptation, and cancer stem cell modulation to chemotherapy resistance [26,[38][39][40][41][42][43]. Also, several recent studies demonstrated the role of FAT10 in chemoresistance [24] and epithelial to mesenchymal transition [25], both of which are associated with cancer polyploidy [44].…”

Section: Discussionmentioning

confidence: 63%

Cisplatin resistant ovarian cancer cells reveal a polyploid phenotype with remarkable activation of nuclear processes

Adibi

Moein

Gheisari

2021

Preprint

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Background Tumor recurrence as a main cause of cancer death is a big barrier in cancer complete treatment. Various studies denote for the possible role of therapeutics in tumor relapse. Cisplatin as one of the generally-used chemotherapy agents is supposed to be the source of therapy-resistance through formation of polyploid giant cancer cells (PGCCs). Nevertheless, the mechanisms by which PGCCs promote tumor relapse are not fully understood.Methods In this study we performed experimental and bioinformatic investigations to recognize the mechanisms related to cisplatin resistance. A2780 and SCOV-3 cell lines were treated with cisplatin for 72 hours and were evaluated for their morphology by fluorescent microscopy and DNA content analysis. Furthermore, a microarray dataset of cisplatin-resistant ovarian cancer cells was reanalyzed to determine the significantly altered genes and signaling pathways.Result Although cisplatin led to death of considerable fraction of cells in both cell lines, a significant number of survived cells became polyploid. On the other hand, our high throughput analysis determined significant change in expression of 1930 genes which mainly related to gene regulatory mechanisms and nuclear processes. Besides, mTOR, hypoxia, Hippo and 14-3-3 signaling pathways previously shown to have role in PGCCs were determined.Conclusion Taken together, results of this study demonstrated some key biological mechanisms related to cisplatin-resistant polyploid cancer cells.

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Section: Discussionmentioning

confidence: 63%

Cisplatin resistant ovarian cancer cells reveal a polyploid phenotype with remarkable activation of nuclear processes

Adibi

Moein

Gheisari

2021

Preprint

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“…Recently, research suggests that ccRCC is a metabolic disease with metabolic reprogramming covering a wide range of biological processes, such as fatty acid metabolism, aerobic glycolysis and amino acid metabolism [49]. As a key pathway for protein degradation, UPS is also reported to be an essential modulator of cancer metabolism [50]. Obviously, there requires more studies and efforts focusing on this field to develop novel diagnostic and therapeutic methods.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective

Guo¹,

Li²,

Liu³

et al. 2021

J. Cancer

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Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system. The ubiquitin proteasome system (UPS) plays an important role in the generation, metabolism and survival of tumor. We are aimed to make a comprehensive exploration of the UPS's role in ccRCC with bioinformatic tools, which may contribute to the understanding of UPS in ccRCC, and give insight for further research. Methods: The UPS-related genes (UPSs) were collected by an integrative approach. The expression and clinical data were downloaded from TCGA database. R soft was used to perform the differentially expressed UPSs analysis, functional enrichment analysis. We also estimated prognostic value of each UPS with the help of GEPIA database. Two predicting models were constructed with the differentially expressed UPSs and prognosis-related genes, respectively. The correlations of risk score with clinical characteristics were also evaluated. Data of GSE29609 cohort were obtained from GEO database to validate the prognostic models. Results: We finally identified 91 differentially expressed UPSs, 48 prognosis related genes among them, and constructed a prognostic model with 18 UPSs successfully, the AUC was 0.760. With the help of GEPIA, we found 391 prognosis-related UPSs, accounting for 57.84% of all UPSs. Another prognostic model was constructed with 28 prognosis-related genes of them, and with a better AUC of 0.825. Additionally, our models can also stratify patients into high and low risk groups accurately in GSE29609 cohort. Similar prognostic values of our models were observed in the validated GSE29609 cohort. Conclusions: UPS is dysregulated in ccRCC. UPS related genes have significant prognostic value in ccRCC. Models constructed with UPSs are effective and applicable. An abnormal ubiquitin proteasome system should play an important role in ccRCC and be worthy of further study.

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“…From this aspect, controlling cancer energy metabolism becomes a potential treatment. Besides, APC/C CDC20 as an E3 ubiquitin ligase can also promote substrate ubiquitination and their subsequent degradation by the proteasome, which can regulate metabolic signaling pathways, transcription factors, and metabolic enzymes [52]. These show that CDC20 attaches great importance to OC and can be a speci c target to treat OC.…”

Section: Discussionmentioning

confidence: 99%

CDC20 as a new therapeutic target for treating ovarian cancer: an integrated bioinformatics analysis

Zhang

Yang

2021

Preprint

Self Cite

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Background: There were 313959 cases of newly diagnosed ovarian cancer (OC) and 207252 new deaths for OC in 2020 and OC lacks effective treatment options. Therefore, identifying novel therapeutic targets is imminent. Here, we use an integrated bioinformatics analysis to key genes involved in ovarian cancer and reveal potential therapeutic targets.Methods: GSE105437, GSE14407 and GSE18520 downloaded from Gene Expression Omnibus (GEO) were used to screen differentially expressed genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the DEGs. Protein-protein interaction network (PPI) was drawn through STRING database and select CDC20 having the highest degrees of connectivity as the potential therapeutic target. Oncomine database and quantitative Real-time RT-PCR (RT-qPCR) of the ovarian tissues were used to validate the mRNA expression of CDC20. We use Gene Set Enrichment Analysis (GSEA) software to explore the potential biological function of CDC20 in OC. Results: A total of 821 DEGs were obtained, including 497 upregulated genes and 324 downregulated genes. Functional and pathway enrichment analyses indicated the DEGs were mainly involved in DNA-binding transcription activator activity, tubulin binding, microtubule binding, cell cycle, Wnt signaling pathway, p53 signaling pathway, and metabolism changes. Oncomine database analysis and RT-qPCR showed that CDC20 is significantly upregulated in OC tissues. GSEA analysis showed that CDC20 may regulate OC via cell cycle, citrate and TCA cycle, Oxidative phosphorylation and ubiquitin mediated proteolysis pathways. Conclusion: The results of the present study deduced that CDC20 is overexpressed in OC and may be a promising therapeutic target for the treatment of OC.

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The role of ubiquitination and deubiquitination in cancer metabolism

Cited by 277 publications

References 306 publications

Cisplatin resistant ovarian cancer cells reveal a polyploid phenotype with remarkable activation of nuclear processes

Cisplatin resistant ovarian cancer cells reveal a polyploid phenotype with remarkable activation of nuclear processes

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective

CDC20 as a new therapeutic target for treating ovarian cancer: an integrated bioinformatics analysis

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