Neddylation pattern indicates tumor microenvironment characterization and predicts prognosis in lung adenocarcinoma DOI Creative Commons
Yuan Yuan Cui,

Zhike Chen,

Bin Pan

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Sept. 13, 2022

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a complex tumor microenvironment. Neddylation, as post-translational modification, plays vital role in development LUAD. To date, no study has explored potential neddylation-associated genes for LUAD classification, prognosis prediction, and treatment response evaluation. Methods: Seventy-six prognostic were identified by Univariate Cox analysis. Patients classified into two patterns based on unsupervised consensus clustering In addition, 10-gene signature was constructed using LASSO-Cox multivariate stepwise regression approach. Results: Substantial differences observed between terms prognosis. Compared neddylation cluster2, cluster1 exhibited low levels immune infiltration that promote progression. Additionally, neddylation-related risk score correlated clinical parameters it can be good predictor patient outcomes, gene mutation levels, chemotherapeutic responses. Conclusion: Neddylation distinguish microenvironment patients Prognostic signatures predict outcomes guide personalized treatment.

Language: Английский

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

25
Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications DOI
Jie Wang, Yian Wang,

Xianjie Jiang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216758 - 216758

Published: Feb. 22, 2024

Language: Английский

Citations

14
Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways DOI Creative Commons
Dequan Liu, Xiangyu Che, Guangzhen Wu

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 8, 2024

Abstract Neddylation is a post-translational modification process, similar to ubiquitination, that controls several biological processes. Notably, it often aberrantly activated in neoplasms and plays critical role the intricate dynamics of tumor microenvironment (TME). This regulatory influence neddylation permeates extensively profoundly within TME, affecting behavior cells, immune angiogenesis, extracellular matrix. Usually, promotes progression towards increased malignancy. In this review, we highlight latest understanding molecular mechanisms target modulate TME by various signaling pathways. There emerging evidence targeted disruption specifically inhibition cullin-RING ligases (CRLs) functionality, presents promising avenue for therapy. MLN4924, small-molecule inhibitor pathway, precisely targets neural precursor cell-expressed developmentally downregulated protein 8 activating enzyme (NAE). recent years, significant advancements have been made field therapy, particularly integration MLN4924 with chemotherapy or combined approach has demonstrated notable success treatment variety hematological solid tumors. Here, investigated inhibitory effects on summarized current therapeutic outcomes against conclusion, review provides comprehensive, up-to-date, thorough overview modifications, offers insight into importance cellular process tumorigenesis.

Language: Английский

Citations

10
Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer DOI Open Access
Kaiqiang Li, Xiao Bai,

Ang-Ting Ke

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116323 - 116323

Published: Feb. 23, 2024

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are elements of the deubiquitinase family, overexpressed in gastric (GC). Through regulation several signaling pathways, such as Wnt/β-Catenin nuclear factor-κB signaling, promotion expression deubiquitination- stabilization-associated proteins, USPs promote proliferation, metastasis, invasion, epithelial-mesenchymal transition GC. In addition, closely related to clinicopathological features, patient prognosis, chemotherapy resistance. therefore could be used prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they not yet been tested clinic. This article provides an overview latest fundamental research on GC, aiming enhance understanding how contribute GC progression, identifying possible targets treatment improve survival.

Language: Английский

Citations

8
Insights on post-translational modifications in fatty liver and fibrosis progression DOI

C. Nageswara Raju,

Kavitha Sankaranarayanan

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167659 - 167659

Published: Jan. 7, 2025

Language: Английский

Citations

1
lncRNA JPX Promotes Tumor Progression by Interacting with and Destabilizing YTHDF2 in Cutaneous Melanoma DOI
Dan Luo, Hui Tang, Liuchang Tan

et al.

Molecular Cancer Research, Journal Year: 2024, Volume and Issue: 22(6), P. 524 - 537

Published: March 5, 2024

Aberrant long noncoding RNAs just proximal to Xist (lncRNA JPX) expression levels have been detected in multiple tumors. However, whether JPX is involved melanoma progression remains unclear. Our study showed that significantly increased tissues and cell lines. To clarify the effect of on cutaneous melanoma, we successfully generated JPX-overexpressing or JPX-knockdown A375 A2058 cells. CCK-8, colony formation EdU, Transwell, cell-cycle phase assays were performed, subcutaneously implanted tumor models used determine function melanoma. The results knockdown reduced proliferation migration malignant cells both vitro vivo. further elucidate molecular mechanism JPX-induced deterioration, performed RNA pull-down, immunoprecipitation, coimmunoprecipitation, Western blot, RNA-sequence analyses. can directly interact with YTHDF2 impede protection from ubiquitin-specific protease 10 (USP10), which promotes its deubiquitination. Thus, decreases protein stability degradation YTHDF2, thereby stabilizing BMP2 mRNA activating AKT phosphorylation. Overall, our revealed a novel ubiquitination, suggesting possibility blocking JPX/USP10/YTHDF2/BMP2 axis as prospective therapeutic approach for

Language: Английский

Citations

5
SUMOylation of annexin A6 retards cell migration and tumor growth by suppressing RHOU/AKT1–involved EMT in hepatocellular carcinoma DOI Creative Commons
Yanfang Yang, Lan Huang, Nan Zhang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 2, 2024

Abstract Background The protein annexin A6 (AnxA6) is involved in numerous membrane-related biological processes including cell migration and invasion by interacting with other proteins. dysfunction of AnxA6, expression abundance change imbalance post-translational modification, tightly related to multiple cancers. Herein we focus on the function AnxA6 SUMOylation hepatocellular carcinoma (HCC) progression. Methods modification sites were identified LC-MS/MS amino acid site mutation. was assessed immunohistochemistry immunofluorescence. HCC cells induced into epithelial-mesenchymal transition (EMT)-featured 100 ng/mL 12-O-tetradecanoylphorbol-13-acetate exposure. ability evaluated under overexpression transwell assay. SUMO1 modified proteins enriched from total cellular immunoprecipitation anti-SUMO1 antibody, then SUMOylated detected Western blot using anti-AnxA6 antibody. nude mouse xenograft orthotopic hepatoma models established determine growth tumorigenicity vivo. patient’s overall survival versus level Kaplan–Meier method. Results Lys579 a major cells, protects degradation via ubiquitin-proteasome pathway. Compared wild-type its SUMO mutant K579R leads disassociation binding RHOU, subsequently RHOU-mediated p-AKT1 ser473 upregulated facilitate EMT progression HCC. Moreover, SENP1 deSUMOylates negatively correlated tissues, high gene ratio ANXA6/SENP1 indicates poor patients. Conclusions deSUMOylation contributes phenotype, combination better tumor biomarker for diagnosis grade malignancy prognosis.

Language: Английский

Citations

5
Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer DOI Creative Commons
Luyao Zhang, Shunfang Liu, Jingliang He

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 18, 2025

The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation UPS implicated hepatocellular carcinoma (HCC), contributing to tumor progression therapeutic resistance. cereblon (CRBN) E3 ubiquitin ligase complex a crucial component UPS, particularly modulating protein response small-molecule modulators like thalidomide. However, endogenous substrates CRBN solid tumors HCC remain poorly characterized. Here, we identify MORF4L1, member MRG family chromatin remodeling damage response, substrate CRBN. Using proteomic analysis, co-immunoprecipitation, structural modeling, demonstrate that promotes MORF4L1 under physiological conditions, which further enhanced by modulator CC-885. Importantly, upregulated multiple cancers, including HCC, suggesting broader role tumorigenesis. Our findings reveal highlight potential targeting cancer.

Language: Английский

Citations

0
Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies DOI

Caizhen Shi,

Bingbing Wang,

Tianyu Zhai

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 20, 2025

Language: Английский

Citations

0
Smurf2 Suppresses Proliferation and Cell Cycle of Triple‐Negative Breast Cancer Cells by Promoting the Polyubiquitination and Degradation of RPL35A DOI Creative Commons

Siyu Wei,

Yuying Liu, Zhihao Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT Human L35a ribosomal protein (RPL35A) has been reported to confer higher drug resistance and viability triple‐negative breast cancer (TNBC) cells, but the mechanism related its promotion of TNBC malignant progression is still unclear. Here, we found that silencing RPL35A could inhibit proliferation cells by suppressing G1/S phase transition. Furthermore, SMAD‐specific E3 ubiquitin ligase 2 (Smurf2) was be a potential upstream RPL35A. Smurf2 interact with promote degradation K63‐linked polyubiquitination, thereby transition cells. In addition, roles were confirmed in xenograft mouse model. Finally, negative correlation between levels human tissues. summary, inhibits blocking cell cycle process, which associated regulating

Language: Английский

Citations

0