UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer DOI Creative Commons

Weiwei Yuan,

Jianye Han,

Zhiheng Wu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 17, 2023

Abstract Background Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes that binds to unstable N-terminal residues of substrate proteins and contributes the formation substrate-linked polyubiquitin chains. However, cellular pathways function in tumors have received inadequate attention. Therefore, aim this study examine potential as prognostic biomarker immunotherapy target for stomach adenocarcinoma (STAD) well its biological molecular mechanism relation disease. Methods Differential expression pan-cancer GSEA analyses were performed using TCGA, GEO GTEx datasets. Immunohistochemical differences between cancer paraneoplastic tissues analyzed HPA database identify enriched AGS cells. Besides, with help Kaplan-Meier curves, univariate multivariate Cox regression, receiver operating characteristic (ROC) curve studies, diagnostic roles can be identified determined. The correlation clinical parameters was predicted TCGA databases. mutation data retrieved from cBioPortal database. mechanisms investigated GO KEGG enrichment analyses. TIMER EPIC computational methods utilized establish connection immune infiltration. Protein determined immunohistochemistry (IHC) Western blot analysis (WB). In regard mRNA expression, Quantitative Real-time PCR (qRT-PCR), it taking advantage (qRT-PCR). Immunoprecipitation (IP) assays used detect protein-protein interactions. Cell proliferation evaluated CCK8 colony assays. invasion wound healing Transwell. Apoptosis flow cytometry. Result upregulated 28 types,including STAD, overexpression validated gastric cell lines tissues. associated advanced pathological characteristics. High linked poor outcomes, including progression-free interval (PFI), overall survival (OS), disease-specific (DSS), surgery, chemotherapy, HER2 expression. significantly correlated parameters, such age, gender, TMN stage, tumor resection, anti-reflux therapy. Amplifications deletions frequent genetic alterations UBR1. According GSEA, several pathways, oxidative phosphorylation, TNF-NFκB pathway. exhibited significant infiltration, direct interaction CD274. Also, STAD cells inhibited due knockdown, but apoptosis promoted contrary way. Conclusion results investigation show overexpressed promoting progression, positively correlates infiltration immunotherapeutic responses. could promising prognosis field STAD.

Language: Английский

Transcription factor BbCDR1 regulates the orchestration between conidial formation and maturation in the entomopathogenic fungus Beauveria bassiana DOI Open Access

Hui Zhang,

Ajing Mao, Yu Liu

et al.

Pest Management Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract BACKGROUND The entomopathogenic fungus Beauveria bassiana has been widely used for pest biocontrol with conidia serving as the main active agents. Conidial yield and quality are two important characteristics in fungal development, however, regulatory mechanisms that orchestrate conidial formation development not well understood. RESULTS In this study, we identified a Zn 2 Cys 6 transcription factor BbCDR1 inhibits production while promoting maturation. Compared wild type, ΔBbCDR1 mutant exhibited 1.88‐fold increase but reduction quality, including decreased cell wall integrity trehalose synthesis. deletion of also led to reduced germination rates under oxidative, osmotic, disruption UV stresses. Interestingly, an virulence 12.5% decrease LT 50 compared type. CONCLUSIONS Further analysis revealed represses expression BbbrlA activates BbwetA , components central developmental pathway (CDP) regulate initiation maturation, respectively. These findings suggest plays crucial role new target gene genetic engineering highly insecticides. © 2025 Society Chemical Industry.

Language: Английский

Citations

1
Succinate Dehydrogenase Subunit C Contributes to Mycelial Growth and Development, Stress Response, and Virulence in the Insect Parasitic Fungus Beauveria bassiana DOI Creative Commons
Jin‐Li Ding, Xiuhui Li, Jiahui Lei

et al.

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(5)

Published: Aug. 16, 2022

The electron transport chain (ETC) is critical for energy supply by mediating the flow along mitochondrial membrane. Succinate dehydrogenase (SDH) also known as complex II in ETC, which SdhC a subunit anchored However, physiological roles of remain enigmatic filamentous fungi.

Language: Английский

Citations

22
N-acetylglucosamine kinase (BbHxk1) has pleiotropic effects on vegetative growth, cell wall integrity, morphological transition, cuticle infection, and metabolic modulation in the biological pesticide Beauveria bassiana DOI
Longbin Zhang,

Wu-Wei-Jie Yang,

Zhihao Yang

et al.

Pesticide Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 203, P. 106015 - 106015

Published: July 3, 2024

Language: Английский

Citations

3
UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer DOI Creative Commons
Weiwei Yuan,

Jianye Han,

Chen Chen

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(16), P. 12029 - 12049

Published: Aug. 23, 2024

Background: Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes that binds to unstable N-terminal residues of substrate proteins and contributes the formation substrate-linked polyubiquitin chains. However, function cellular pathways in tumors have received inadequate attention. This study aimed investigate potential as prognostic biomarker immunotherapy target for stomach adenocarcinoma (STAD) well its biological molecular mechanism relation disease. Methods: Differential expression pan-cancer gene set enrichment analysis (GSEA) were conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue (GTEx) datasets. Human Protein (HPA) database was utilized identify UBR1-enriched AGS cells compare immunohistochemical differences between cancerous adjacent non-cancerous tissues gastric cancer. Quantitative Polymerase Chain Reaction (QPCR) Western blot (WB) analyses employed validate these findings both GES-1 four cancer cell lines assessed QPCR WB. Kaplan-Meier curves, univariate multivariate Cox regression analyses, receiver operating characteristic (ROC) curve performed evaluate diagnostic roles UBR1. Additionally, correlation clinical parameters analyzed TCGA GEO databases. mutation data obtained from cBioPortal database. landscape, mutation-associated genes, structure, tumor burden (TMB), microsatellite instability (MSI) correlations illustrated. functions investigated Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses. immune infiltration TIMER EPIC computational methods. levels determined immunohistochemistry (IHC) WB analysis. real-time PCR (qRT-PCR) analyze mRNA expression. Immunoprecipitation (IP) assays detect protein-protein interactions PDL1, while immunofluorescence used observe co-localization proteins. Cell proliferation evaluated CCK8 colony assays. migration Transwell wound healing Finally, apoptosis flow cytometry, changes apoptotic NF-κB P65 pathway Results: upregulated 28 types, including STAD, overexpression validated tissues. associated with advanced pathological characteristics. High linked poor outcomes, overall survival (OS), progression-free interval (PFI), disease-specific (DSS), responses surgery, chemotherapy, HER2 showed significant such age, gender, TNM stage, resection, anti-reflux therapy. Amplifications deletions most frequent genetic alterations According KEGG GSEA significantly several pathways, oxidative phosphorylation, TNF-NFκB pathway. also exhibited immunotherapy, direct interaction PDL1. Knockdown inhibited proliferation, migration, invasion STAD promoted apoptosis. Conclusions: overexpressed promoting progression positively correlating immunotherapeutic responses. Therefore, could be promising prognosis STAD.

Language: Английский

Citations

2
Essential Role of COP9 Signalosome Subunit 5 (Csn5) in Insect Pathogenicity and Asexual Development of Beauveria bassiana DOI Creative Commons

Ya‐Ni Mou,

Kang Ren,

Sen‐Miao Tong

et al.

Journal of Fungi, Journal Year: 2021, Volume and Issue: 7(8), P. 642 - 642

Published: Aug. 7, 2021

Csn5 is a subunit ofthe COP9/signalosome complex in model fungi. Here, we report heavier accumulation of orthologous the nucleus than cytoplasm and its indispensability to insect pathogenicity virulence-related cellular events Beauveria bassiana. Deletion csn5 led 68% increase intracellular ubiquitin dysregulation 18 genes encoding ubiquitin-activating (E1), -conjugating (E2), -ligating (E3) enzymes ubiquitin-specific proteases, suggesting role balanced ubiquitination/deubiquitination. Consequently, deletion mutant displayed abolished pathogenicity, marked reductions conidial hydrophobicity adherence cuticle, secretion cuticle penetration-required enzymes, blocked haemocoel colonisation, reduced conidiation capacity despite unaffected biomass accumulation. These phenotypes correlated well with sharply repressed or expressions key hydrophobin required for biosynthesis/assembly developmental activator essential aerial submerged blastospore production. In mutant, increased sensitivities heat shock oxidative stress also expression levels several heat-responsive decreased activities antioxidant enzymes. Altogether, Csn5-reliant ubiquitination/deubiquitination balance coordinates those crucial quality control functionally important which are collectively fungal events, asexual development.

Language: Английский

Citations

9
Dsk2 involves in conidiation, multi‐stress tolerance and thermal adaptation in Beauveria bassiana DOI
Dingyi Wang, Chao Lv, Yi Guan

et al.

Environmental Microbiology Reports, Journal Year: 2021, Volume and Issue: 13(3), P. 384 - 393

Published: April 18, 2021

Summary Dsk2 is a nuclear‐enriched ubiquitin‐like polyubiquitin‐binding protein that regulates degradation in yeast but has not been explored yet filamentous fungi, such as Beauveria bassiana . Here, we report located both the nucleus and cytoplasm of hyphal cells. Deletion resulted mild growth defect on scant media with various carbon/nitrogen sources dramatic attenuation conidiation capability at optimal condition. Compared to wild‐type, Δ strains are much more sensitive high osmotic oxidative pressure during vegetative growth. Meanwhile, mutant showed an increased chemical tolerance Congo red calcofluor white, two cell wall perturbing agents. The transcriptional changes genes involved central development, superoxide dismutase chitin synthesis pathway indicate acts multi‐functional regulator adapting environmental changes. Importantly, negatively regulated ability thermal resistance B , which makes it potential target gene for constructing engineering anti‐thermal circumstance global warming. Altogether, our finding highlights novel roles asexual cycle, multi‐stress pest control

Language: Английский

Citations

4
The Deubiquitinating Enzyme MrUbp14 Is Involved in Conidiation, Stress Response, and Pathogenicity in Metarhizium robertsii DOI Creative Commons
Zhangxun Wang, Hua Chen, Hao Li

et al.

Frontiers in Fungal Biology, Journal Year: 2022, Volume and Issue: 3

Published: May 16, 2022

Protein ubiquitination, which is involved in various biological processes eukaryotic cells, a reversible modification of proteins. Deubiquitinases can maintain ubiquitin homeostasis by removing or modulating protein degradation via the ubiquitin-proteasome system (UPS). Metarhizium robertsii, an entomopathogenic fungus, has become model fungus for investigating interactions between insects and fungal pathogens. To explore possible effects deubiquitination process on development, stress response, virulence M. disruption MrUbp14 (an ortholog yeast ubiquitin-specific protease gene, Ubp14) was performed. The results this study showed that deletion led to accelerated conidial germination, reduced yields, decreased expression levels some genes conidiation. Furthermore, mutant (ΔMrUbp14) exhibited tolerance cell wall-damaging stressors (Congo red SDS) heat stress. Importantly, bioassay demonstrated ΔMrUbp14 strain largely cuticle infection, but not direct injection, accompanied significant decline appressorium formation penetration. Moreover, our resulted significantly increased ubiquitination total protein, suggesting acts as deubiquitinating enzyme robertsii. In summary, phenotypic changes gene mutants suggest important conidiation,

Language: Английский

Citations

3
Rad6 Regulates Conidiation by Affecting the Biotin Metabolism in Beauveria bassiana DOI Creative Commons
Yuhan Guo,

Haomin He,

Yi Guan

et al.

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(9), P. 613 - 613

Published: Aug. 28, 2024

Rad6 is a canonical ubiquitin-conjugating enzyme known for its role in regulating chromosome-related cellular processes yeast and has been proven to have multiple functions

Language: Английский

Citations

0
Glutamate metabolism disruption in Johanson–Blizzard syndrome: Insights from C. elegans ubr-1 model DOI

Yi Li,

Shangbang Gao

Journal of Biosciences, Journal Year: 2024, Volume and Issue: 50(1)

Published: Dec. 20, 2024

Language: Английский

Citations

0
UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer DOI Creative Commons

Weiwei Yuan,

Jianye Han,

Zhiheng Wu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 17, 2023

Abstract Background Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes that binds to unstable N-terminal residues of substrate proteins and contributes the formation substrate-linked polyubiquitin chains. However, cellular pathways function in tumors have received inadequate attention. Therefore, aim this study examine potential as prognostic biomarker immunotherapy target for stomach adenocarcinoma (STAD) well its biological molecular mechanism relation disease. Methods Differential expression pan-cancer GSEA analyses were performed using TCGA, GEO GTEx datasets. Immunohistochemical differences between cancer paraneoplastic tissues analyzed HPA database identify enriched AGS cells. Besides, with help Kaplan-Meier curves, univariate multivariate Cox regression, receiver operating characteristic (ROC) curve studies, diagnostic roles can be identified determined. The correlation clinical parameters was predicted TCGA databases. mutation data retrieved from cBioPortal database. mechanisms investigated GO KEGG enrichment analyses. TIMER EPIC computational methods utilized establish connection immune infiltration. Protein determined immunohistochemistry (IHC) Western blot analysis (WB). In regard mRNA expression, Quantitative Real-time PCR (qRT-PCR), it taking advantage (qRT-PCR). Immunoprecipitation (IP) assays used detect protein-protein interactions. Cell proliferation evaluated CCK8 colony assays. invasion wound healing Transwell. Apoptosis flow cytometry. Result upregulated 28 types,including STAD, overexpression validated gastric cell lines tissues. associated advanced pathological characteristics. High linked poor outcomes, including progression-free interval (PFI), overall survival (OS), disease-specific (DSS), surgery, chemotherapy, HER2 expression. significantly correlated parameters, such age, gender, TMN stage, tumor resection, anti-reflux therapy. Amplifications deletions frequent genetic alterations UBR1. According GSEA, several pathways, oxidative phosphorylation, TNF-NFκB pathway. exhibited significant infiltration, direct interaction CD274. Also, STAD cells inhibited due knockdown, but apoptosis promoted contrary way. Conclusion results investigation show overexpressed promoting progression, positively correlates infiltration immunotherapeutic responses. could promising prognosis field STAD.

Language: Английский

Citations

0