Ubiquitin levels: the next target against gynecological cancers?

Haakonsen, Diane L.; Rapé, Michael

doi:10.1172/jci98262

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…UBC and UBB are mainly involved in the ubiquitination of eukaryotic cells, a series of processes including protein degradation, DNA repair, transcription, protein transport, cell cycle regulation, and signal transduction. Many of these processes are crucial for cancer cell survival . We believe that the ultimate role of LGR6 in the pathogenesis of cancer is the result of the integration of all of its biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…Through further analysis of the LGR6 PPI network and KEGG pathways, we found that LGR6 interacts with RSPO1, RSPO2, RSPO3, and RSPO4 (interaction score ≧0.967), and LGR6 primarily participates in the Wnt/β‐catenin signaling pathway to exert its biological functions. LGR6 interacts with its ligand RSPO1‐4 to activate the Wnt/β‐catenin signaling pathway through phosphorylation, thereby affecting multipotent biological functions …”

Section: Discussionmentioning

confidence: 99%

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LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma

Chai

Shen

Zhang

et al. 2020

Clinical Laboratory Analysis

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Background Leucine‐rich repeat–coupled receptor 6 (LGR6) is a marker of the skin, nails, and other types of adult tissue stem cells and has been widely found to be related to the development and progression of a variety of cancer types. The clinical significance and biological function of LGR6 in esophageal squamous cell carcinoma (ESCC) have not been determined. Methods The expression of LGR6 at the transcriptional level was analyzed by searching the TCGA and UCSC data sets. Immunohistochemistry, WB, and q‐PCR were used to detect the expression of LGR6 in ESCC and adjacent normal tissues. LGR6 PPI networks and KEGG pathways were used to analyze the potential biological functions of LGR6. Results The expression of LGR6 in ESCC tissues was significantly higher than that in normal tissues and was negatively correlated with the differentiation degree of ESCC and the prognosis of the patients but not closely correlated with the TNM stage of ESCC. PPI networks showed that LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4. KEGG pathway analysis showed that LGR6 activated the Wnt/β‐catenin signaling pathway by binding with RSPO ligands to promote the progression of ESCC. Conclusion LGR6 can serve as a potential diagnostic and prognostic marker for ESCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma

Chai

Shen

Zhang

et al. 2020

Clinical Laboratory Analysis

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“…Besides, we noticed that a batch of important genes such as UBB, UBE2C, FBXO21, USP53 and UBE2E3 were significantly changed in CLL-1 knock-out cells and enriched in ubiquitination related GO terms and pathways, which indicated that CLL-1 might regulate ubiquitination in AML. Ubiquitination is an essential post-translational modification involved in protein stability, localization, interactions, and activity, which influences cell apoptosis, cell survival, cell-cycle progression, DNA repair and antigen presentation, and is implicated in multiple pathophysiological states and diseases such as cancer, infections and hereditary disorders (van Wijk, Fulda, Dikic, & Heilemann, 2019).Ubiquitination is mediated by the sequential action of ubiquitin-activating enzyme, ubiquitin-conjugating enzyme and ubiquitin protein ligase (Manasanch & Orlowski, 2017), and the abundance of cellular ubiquitin is modulated by a family of multiple ubiquitin genes such as UBB and UBC (Haakonsen & Rape, 2017). UBB has been implicated in many tumors including ovarian cancer, gastric cancer, lung adenocarcinoma, etc (Deng, Huang, Wang, & Chen, 2020;Gong, Lin, & Yuan, 2020;Scarpa et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

Fang

Jun

et al. 2022

Preprint

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CLL-1 has been revealed its potential role in acute myeloid leukemia (AML), however, the underlying mechanisms remain unclear. CRISPR/Cas9 strategy was employed to knock out CLL-1 gene in U937 cells and western-blot was used to validate the success of knock out. CCK8 and Transwell assays were used to detect cells viability and migration, respectively. RNA-sequencing was performed to profile mRNA expression in CLL-1 gene knock-out and wide type U937 cells. A cutoff of 1.5-fold change and false discovery rate (FDR)<0.05 was used to screen differentially expressed genes (DEGs), which were presented by volcano plots and hierarchical cluster heatmap. Protein-protein interaction (PPI) network was constructed by String database and Cytoscape software. Furthermore, hub genes were mined by CytoNCA and MCODE, which were subjected to functional enrichment using R package. Finally, the findings were validated using qRT-PCR and western-blot. The protein level of CLL-1 was significantly lowered, and cell viability and migration were suppressed in knock-out cells compared to wide type. Using RNA-sequencing and bioinformatics analysis, 452 DEGs (179 up-regulated and 273 down-regulated) were obtained, and several important hub genes (such as CCR2, FBXO21, UBB and UBE2C) were filtered out, which were enriched in 132 GO terms and 36 KEGG pathways such as chemokine signaling pathway and ubiquitin mediated proteolysis. A total of 8 representative genes mRNA expressions were validated by qRT-PCR, and the protein levels of 6 genes were confirmed by western-blot. CLL-1 gene might exert its role in AML through modulating genes enriched in multiple functions such as chemokine signaling and ubiquitination. Our results may give us new knowledge of CLL-1 in AML and provide a basis for mining novel targets.

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“…Ubiquitin is involved in several cellular processes, and aberrant events in ubiquitin-mediated processes promote the carcinogenesis and progression of NSCLC [ 24 ]. UBB is strongly suppressed in some cancers, including endometrial carcinoma and ovarian cancer [ 25 ]. Tang et al revealed that ubiquitin was highly expressed in NSCLC tissues; however, increased ubiquitin was attributed to the increased transcripts of ubiquitin C (UBC) rather than UBB .…”

Section: Discussionmentioning

confidence: 99%

High Expression of UBB, RAC1, and ITGB1 Predicts Worse Prognosis among Nonsmoking Patients with Lung Adenocarcinoma through Bioinformatics Analysis

Deng

Huang²,

Wang

et al. 2020

BioMed Research International

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Purpose. The molecular mechanism underlying the tumorigenesis and progression of lung adenocarcinoma (LUAD) in nonsmoking patients remains unclear. This study was conducted to select crucial therapeutic and prognostic biomarkers for nonsmoking patients with LUAD. Methods. Microarray datasets from the Gene Expression Omnibus (GSE32863 and GSE75037) were analyzed for differentially expressed genes (DEGs). Gene Ontology (GO) enrichment analysis of DEGs was performed, and protein-protein interaction network was then constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. Hub genes were then identified by the rank of degree. Overall survival (OS) analyses of hub genes were performed among nonsmoking patients with LUAD in Kaplan-Meier plotter. The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) databases were applied to verify hub genes. In addition, we performed Gene Set Enrichment Analysis (GSEA) of hub genes. Results. We identified 1283 DEGs, including 743 downregulated and 540 upregulated genes. GO enrichment analyses showed that DEGs were significantly enriched in collagen-containing extracellular matrix and extracellular matrix organization. Moreover, 19 hub genes were identified, and 12 hub genes were closely associated with OS. Although no obvious difference was detected in ITGB1, the downregulation of UBB and upregulation of RAC1 were observed in LUAD tissues of nonsmoking patients. Immunohistochemistry in THPA database confirmed that UBB and ITGB1 were downregulated, while RAC1 was upregulated in LUAD. GSEA suggested that ribosome, B cell receptor signaling pathway, and cell cycle were associated with UBB, RAC1, and ITGB1 expression, respectively. Conclusions. Our study provides insights into the underlying molecular mechanisms of the carcinogenesis and progression of LUAD in nonsmoking patients and demonstrated UBB, RAC1, and ITGB1 as therapeutic and prognostic indicators for nonsmoking LUAD. This is the first study to report the crucial role of UBB in nonsmoking LUAD.

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Ubiquitin levels: the next target against gynecological cancers?

Cited by 10 publications

References 17 publications

LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma

LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

High Expression of UBB, RAC1, and ITGB1 Predicts Worse Prognosis among Nonsmoking Patients with Lung Adenocarcinoma through Bioinformatics Analysis

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