Ubiquitin D Promotes Progression of Oral Squamous Cell Carcinoma via NF-Kappa B Signaling

An, Shi; Wang, Yi; Feng, Jinping; Yan, Enshi; Zhou, Jiacheng; Ye, Jinhai; Zhang, Hongchuan; Ding, Xu; Li, Gang; Wu, Yunong; Zheng, Yang; Song, Xiaomeng

doi:10.14348/molcells.2021.2229

Cited by 14 publications

(11 citation statements)

References 50 publications

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“…Ubiquitin-fold modifier 1 (UFM1) is a newly discovered ubiquitin-like protein ( Komatsu et al, 2004 ). Like ubiquitin and other ubiquitin-like proteins ( Song et al, 2021 ), UFM1 is conjugated to target proteins by a three-step enzyme system: UBA5, a UFM1-activating E1 enzyme; UFC1, a UFM1-conjugating E2 enzymes; and UFL1, a UFM1 E3 ligases ( Daniel and Liebau, 2014 ; Komatsu et al, 2004 ; Yoo et al, 2015 ). In addition, a UFM1-binding protein (UFBP1, also known as DDRGK1) is required for protein modification by UFM1 ( Yoo et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

Yoo

Park

Kim

et al. 2022

Molecules and Cells

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The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

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Section: Introductionmentioning

confidence: 99%

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

Yoo

Park

Kim

et al. 2022

Molecules and Cells

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“…The nomogram could help to screen for high-risk patients and determine more aggressive treatment regimens for high-risk patients with glioma (31,32). Although few study show that UBD expression could be a prognostic factor for glioma, a large number of relevant studies have revealed that UBD expression could be an adverse prognostic biomarker for various tumors (11,13,33,34). These results suggest that UBD has the potential to become a diagnostic marker in various cancers.…”

Section: Discussionmentioning

confidence: 99%

UBD is a potential diagnostic and prognostic biomarker in glioma

Yang

Xie

et al. 2022

Preprint

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Background: Several studies had shown that the ubiquitin D (UBD) could be a potential prognostic factor in various cancers. However, the prognostic value of UBD in glioma remained unknown. Materials and Methods: The differences of UBD expression in glioma were analyzed based on the datasets of the Cancer Genome Atlas database (TCGA) and Chinese Glioma Genome Atlas (CGGA) and identified by qRT-PCR and western blot. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene set enrichment analysis (GSEA) were used to determine the functions of UBD. Moreover, the protein network of UBD was constructed using Cytoscape software. A spearman’s correlation analysis was performed to determine the association between UBD expression and immune cell infiltration. Additionally, a logistic regression analysis was performed to analyze the association between UBD expression and the clinicopathological characteristics of the glioma patients. The diagnostic and prognostic predictive values of UBD were evaluated using the Kaplan–Meier survival curves, Cox regression analysis, diagnostic receiver operating characteristic (ROC) curves, and nomogram model. Finally, the biological function of UBD was determined by wound healing assays, transwell assays, EdU and colony formation assays. Results: UBD expression in glioma samples was considerably increased, which was associated with the P53 pathway, angiogenesis, inflammatory response, TNFα -NF-κB signaling, IL-6-JAK-STAT3 signaling, PI3K-AKT-mTOR signaling, TGF-β signaling, KRAS signaling, as well as hypoxia, and epithelial-mesenchymal transition (EMT). UBD expression correlated with the infiltration level of immune cells through the ssGSEA method. High UBD expression was an independent prognostic factor of glioma in TCGA. ROC curve analysis showed good diagnostic efficacy of UBD in glioma. Furthermore, UBD could increase the migration, invasion and proliferation ability of glioma cells. Conclusion: UBD may be a potential prognostic marker and therapeutic target in glioma.

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Section: Discussionmentioning

confidence: 99%

“…UBD modulates various signaling pathways involved in tumor development, such as NF-κB and Wnt/β-catenin signaling pathways ( 16 , 50 ). Notably, UBD accelerates the progression of oral squamous cell carcinoma via NF-κB signaling ( 50 ). Elevated UBD expression has been shown to drive the invasion and metastasis of hepatocellular carcinoma cells by binding to β-catenin to prevent its ubiquitylation and degradation ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway

et al. 2023

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Ubiquitin D (UBD), a member of the ubiquitin-like modifier family, has been reported to be highly expressed in various types of cancer and its overexpression is positively associated with tumor progression. However, the role and mechanism of UBD in rheumatoid arthritis (RA) remain elusive. In the present study, the gene expression profiles of GSE55457 were downloaded from the Gene Expression Omnibus database to assess differentially expressed genes and perform functional enrichment analyses. UBD was overexpressed by lentivirus transfection. The protein level of UBD, p-p38 and p38 in RA-fibroblast-like synoviocytes (FLSs) were examined by western blotting. Cell Counting Kit-8 and flow cytometry assays were used to detect the functional changes of RA-FLSs transfected with UBD and MAPK inhibitor SB202190. The concentrations of inflammatory factors (IL-2, IL-6, IL-10 and TNF-α) were evaluated using ELISA kits. The results revealed that UBD was overexpressed in RA tissues compared with in the healthy control tissues. Functionally, UBD significantly accelerated the viability and proliferation of RA-FLSs, whereas it inhibited their apoptosis. Furthermore, UBD significantly promoted the secretion of inflammatory factors (IL-2, IL-6, IL-10 and TNF-α). Mechanistically, elevated UBD activated phospohorylated-p38 in RA-FLSs. By contrast, UBD overexpression and treatment with the p38 MAPK inhibitor SB202190 not only partially relieved the UBD-dependent effects on cell viability and proliferation, but also reversed its inhibitory effects on cell apoptosis. Furthermore, SB202190 partially inhibited the effects of UBD overexpression on the enhanced secretion of inflammatory factors. The present study indicated that UBD may mediate the activation of p38 MAPK, thereby facilitating the proliferation of RA-FLSs and ultimately promoting the progression of RA. Therefore, UBD may be considered a potential therapeutic target and a promising prognostic biomarker for RA.

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Ubiquitin D Promotes Progression of Oral Squamous Cell Carcinoma via NF-Kappa B Signaling

Cited by 14 publications

References 50 publications

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

UBD is a potential diagnostic and prognostic biomarker in glioma

Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway

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