RNF26-mediated ubiquitination of TRIM21 promotes bladder cancer progression DOI
Dongwei Yao, Feng Xin, Xiaozhou He

et al.

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(8), P. 4082 - 4095

Published: Jan. 1, 2024

RNF26 is an important E3 ubiquitin ligase that has been associated with poor prognosis in bladder cancer. However, the underlying mechanisms of cancer tumorigenesis are not fully understood. In present study, we found expression level was significantly upregulated tissues, and higher closely poorer prognosis, lower immune cell infiltration, more sensitive to checkpoint blockade drugs chemotherapy drugs, including cisplatin, VEGFR-targeting MET-targeting drugs. knockdown UMUC3 T24 lines inhibited growth, colony formation migratory capacity. Meanwhile, overexpression had opposite effects. Mechanistically, exerts its oncogenic function by binding TRIM21 promoting ubiquitination subsequent degradation. Moreover, revealed ZHX3 as a downstream target RNF26/TRIM21 pathway Taken together, identified novel RNF26/TRIM21/ZHX3 axis promotes progression. Thus, constitutes potential efficacy predictive marker may serve therapeutic for treatment

Language: Английский

Novel post-translational modification learning signature reveals B4GALT2 as an immune exclusion regulator in lung adenocarcinoma DOI Creative Commons
Zhenfa Zhang, Dingli Wang, Guangyao Zhou

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010787 - e010787

Published: Feb. 1, 2025

Background Lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment efficacy evaluation. While post-translational modifications are known to influence tumor progression, their prognostic value LUAD remains largely unexplored. Methods We developed a modification learning signature (PTMLS) using machine techniques, analyzing data from 1231 patients across seven global cohorts. The signature’s predicting immunotherapy response was evaluated 12 cohorts spanning multiple cancer types (n=1201). An in-house tissue cohort (n=171) used validate beta-1,4-galactosyltransferase 2’s (B4GALT2’s) significance. role of B4GALT2 immune exclusion investigated through vivo vitro experiments. Results established PTMLS exhibited exceptional predictive capabilities patient outcomes, surpassing the 98 existing indicators. system’s validated diverse malignancy categories for immunotherapeutic assessment. From biological perspective, correlations were observed between immunological parameters, whereby elevated levels characterized by attenuated responses immunologically cold neoplastic features. Within framework, identified as crucial molecular component (r=0.82, p<0.05), its heightened expression linked unfavorable clinical outcomes cases, particularly specimens exhibiting CD8-depleted phenotypes. spatial distribution patterns cell populations, specifically CD8+ T lymphocytes CD20+ B lymphocytes, elucidated multiplexed immunofluorescence analysis. Laboratory investigations subsequently B4GALT2’s regulatory on cellular expansion both laboratory cultures animal models. Significantly, suppression found enhance lymphocyte populations functional status, thereby potentiating anti-programmed death protein 1 studies. This phenomenon reduced CD62L+CD8 alongside GZMB+/CD44+/CD69+CD8 populations. Conclusion system represents an effective instrument individualized evaluation stratification identification previously unrecognized oncogenic factor involved novel therapeutic avenue optimization.

Language: Английский

Citations

5
Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy DOI Creative Commons
Daniela Spano, Giuliana Catara

Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 29 - 29

Published: Dec. 22, 2023

Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects various signaling pathways. can alter molecular functions tagged substrates respect protein turnover, biological activity, subcellular localization or protein–protein interaction. As result, wide variety cellular processes are under ubiquitination-mediated control, contributing maintenance homeostasis. It follows that dysregulation ubiquitination reactions plays relevant role in pathogenic states human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, enzymes ubiquitin–proteasome system (UPS), including E3 ligases deubiquitinases (DUBs), have attracted attention novel druggable targets for development new anticancer therapeutic approaches. This perspective article summarizes peculiarities shared by involved reaction which, when deregulated, lead tumorigenesis. Accordingly, an overview main pharmacological interventions targeting UPS clinical use still trials provided, also highlighting limitations efficacy these Therefore, attempts circumvent drug resistance side well UPS-related emerging technologies therapeutics discussed.

Language: Английский

Citations

29
E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies DOI Creative Commons
Maoyu Wang, Zhensheng Zhang, Zhizhou Li

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 11, 2023

With the rapidly increasing incidence of bladder cancer in China and worldwide, great efforts have been made to understand detailed mechanism tumorigenesis. Recently, introduction immune checkpoint inhibitor-based immunotherapy has changed treatment strategy for cancer, especially advanced improved survival patients. The ubiquitin–proteasome system, which affects many biological processes, plays an important role cancer. Several E3 ubiquitin ligases deubiquitinases target checkpoints, either directly or indirectly. In this review, we summarize recent progress tumorigenesis further highlight implications immunotherapies.

Language: Английский

Citations

8
ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway DOI Creative Commons
Tingjun Wang, Gang Wang,

Danni Shan

et al.

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(11), P. 3297 - 3312

Published: Jan. 1, 2024

Acetyl-CoA acetyltransferase 1 (ACAT1) plays a significant role in the regulation of gene expression and tumorigenesis.However, biological ACAT1 bladder cancer (BLCA) has yet to be elucidated.This research aimed elucidate bioinformatics features functions BLCA.Here, we demonstrate that is elevated BLCA tissues correlated with specific clinicopathological an unfavorable prognosis for survival patients.ACAT1 was identified as independent risk factor BLCA.Phenotypically, both vitro vivo, knockdown suppressed cell proliferation migration, while overexpression had opposite effect.Mechanistic assays revealed enhances metastasis through AKT/GSK3β/c-Myc signaling pathway by modulating cycle EMT.Taken together, results our study reveal oncogenic driver tumor metastasis, indicating its potential diagnostic therapeutic target this disease.

Language: Английский

Citations

2
The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy DOI Creative Commons
Yongmei Wang, Saisai Li, Wenqin Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 9, 2024

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through regulation protein degradation function. By influencing expression checkpoint-associated proteins, UPS modulates T cell-mediated anti-tumor responses can potentially facilitate escape tumor cells. Additionally, contributes to remodeling immunosuppressive microenvironment (TIME) by regulating B cells, dendritic (DCs), macrophages, Treg Targeting conjunction with combining these other therapeutic approaches, may significantly enhance efficacy combination therapies pave way for novel cancer treatment strategies. In this review, we first summarize composition alterations TIME, particular emphasis on TIME its interactions various cell types. Finally, explore potential UPS-targeted immunotherapy substantially improve effectiveness patient survival outcomes.

Language: Английский

Citations

2
RNF26-mediated ubiquitination of TRIM21 promotes bladder cancer progression DOI
Dongwei Yao, Feng Xin, Xiaozhou He

et al.

American Journal of Cancer Research, Journal Year: 2024, Volume and Issue: 14(8), P. 4082 - 4095

Published: Jan. 1, 2024

RNF26 is an important E3 ubiquitin ligase that has been associated with poor prognosis in bladder cancer. However, the underlying mechanisms of cancer tumorigenesis are not fully understood. In present study, we found expression level was significantly upregulated tissues, and higher closely poorer prognosis, lower immune cell infiltration, more sensitive to checkpoint blockade drugs chemotherapy drugs, including cisplatin, VEGFR-targeting MET-targeting drugs. knockdown UMUC3 T24 lines inhibited growth, colony formation migratory capacity. Meanwhile, overexpression had opposite effects. Mechanistically, exerts its oncogenic function by binding TRIM21 promoting ubiquitination subsequent degradation. Moreover, revealed ZHX3 as a downstream target RNF26/TRIM21 pathway Taken together, identified novel RNF26/TRIM21/ZHX3 axis promotes progression. Thus, constitutes potential efficacy predictive marker may serve therapeutic for treatment

Language: Английский

Citations

1