Ubiquitination-related biomarkers in metastatic melanoma patients and their roles in tumor microenvironment DOI Creative Commons
Zhang Li, Zhehao Shi, Fan Zhang

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: May 19, 2023

Skin cutaneous melanoma (SKCM) is the deadliest type of malignancy. Ubiquitination a process protein sorting and degradation that exhibits multiple functions in progression various tumors. This study aimed to characterize set genes for ubiquitination SKCM.The expression patterns ubiquitin-associated (URGs) corresponding clinical information SKCM tissues were comprehensively analyzed based on The Cancer Genome Atlas (TCGA) database. We performed univariate multivariate Cox proportional regression models risk scores identify four critical related prognostic (HCLS1, CORO1A, NCF1 CCRL2), which used construct signatures. also studied effects HCLS1, CORO1A CCRL2 tumor metastasis-related indicators at cellular level through vitro experiments.SKCM patients low-risk group showing longer survival than those high-risk group. Characteristic correlated with several clinicopathological variables reflected infiltration immune cells. In addition, knockdown CLS1, affected malignant biological behavior EMT signaling pathway.This provides novel prospective strategy improve patients.

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

27
The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy DOI Creative Commons
Bo Hou, Ting Chen, He Zhang

et al.

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

Published: Jan. 17, 2023

The tumor microenvironment (TME) is the surrounding environment, which critical for development and progression. TME also involved in clinical intervention treatment outcomes. Modulation of useful improving therapy strategies. PD-L1 protein on cells interacts with PD-1 T cells, contributing to cell dysfunction exhaustion, blockage immune response. Evidence has demonstrated that expression PD-1/PD-L1 associated response anti-PD-1/PD-L1 cancer patients. It important discuss regulatory machinery how finely regulated cells. In recent years, studies have was governed by various E3 ubiquitin ligases TME, resistance human cancers. this review, we will role molecular mechanisms ligases-mediated regulation TME. Moreover, describe ligases-involved alters efficacy. Altogether, targeting control levels could be a potential strategy potentiate immunotherapeutic effects

Language: Английский

Citations

26
CircRNF10 triggers a positive feedback loop to facilitate progression of glioblastoma via redeploying the ferroptosis defense in GSCs DOI Creative Commons
Chengbin Wang, Minjie Zhang, Yingliang Liu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Sept. 19, 2023

Glioma exhibit heterogeneous susceptibility for targeted ferroptosis. How circRNAs alterations in glioma promote iron metabolism and ferroptosis defense remains unclarified.The highly enriched glioblastoma (GBM) were obtained through analysis of sequencing datasets. Quantitative real-time PCR (qRT-PCR) was used to determine the expression circRNF10 normal brain tissue. Both gain-of-function loss-of-function studies assess effects on using vitro vivo assays. The hypothesis that ZBTB48 promotes established bioinformatics functional RNA pull-down immunoprecipitation (RIP) assays performed examine interaction between target proteins including ZBTB48, MKRN3 IGF2BP3. posttranslational modification mechanism verified coimmunoprecipitation (co-IP) ubiquitination transcription activation HSPB1 IGF2BP3 by confirmed luciferase reporter gene chromatin (ChIP) stabilizing effect explored actinomycin D assay. Finally, a series experiments explore influences progression.A novel circular RNA, hsa_circ_0028912 (named circRNF10), which is significantly upregulated tissues correlated with patients' poor prognosis. Through integrated circRNA-proteins datasets results, we reveal as transcriptional factor binding circRNF10, notably promoting upregulation remodel facilitates launch circRNF10/ZBTB48/IGF2BP3 positive feedback loop GSCs. Additionally, can competitively bind block E3 ubiquitin ligase activity enhance expression. Consequently, circRNF10-overexpressed stem cells (GSCs) display lower Fe2+ accumulation, selectively priming tumors evading.Our research presents abnormal causing molecular metabolic change glioma, leverage discover therapeutically exploitable vulnerability

Language: Английский

Citations

23
p53/MDM2 signaling pathway in aging, senescence and tumorigenesis DOI
Youyi Huang, Xiaofang Che, Peter Wang

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 101, P. 44 - 57

Published: May 17, 2024

Language: Английский

Citations

14
The ubiquitin-proteasome system in the regulation of tumor dormancy and recurrence DOI
Bashar A. Alhasan, А. В. Морозов, Irina V. Guzhova

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189119 - 189119

Published: May 16, 2024

Language: Английский

Citations

7
PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy DOI Creative Commons

Xiaohui Ren,

Lijuan Wang, Likun Liu

et al.

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

Published: April 4, 2024

Immunotherapy has been developed, which harnesses and enhances the innate powers of immune system to fight disease, particularly cancer. PD-1 (programmed death-1) PD-L1 death ligand-1) are key components in regulation system, context cancer immunotherapy. regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation glycosylation. PROTACs (Proteolysis Targeting Chimeras) a type new drug design technology. They specifically engineered molecules that target specific proteins within cell for degradation. have designed demonstrated their inhibitory activity against PD-1/PD-L1 pathway, showed ability degrade proteins. In this review, we describe how improve efficacy could be novel strategy combine with radiotherapy, chemotherapy immunotherapy patients.

Language: Английский

Citations

6
The E3 ubiquitin ligases regulate inflammation in cardiovascular diseases DOI
Xiaohong Chen, Jia Ma, Zhiwei Wang

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 167 - 174

Published: March 3, 2023

Language: Английский

Citations

14
Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy DOI Creative Commons

Xian-Miao Li,

Zhenyu Zhao, Yu Xiao

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: March 30, 2023

Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, acquire mesenchymal properties that mediate invasion metastasis. Stromal soluble mediators tumor microenvironment (TME) exhibit characteristic anti-inflammatory protumorigenic activities. Ubiquitination, is an essential reversible posttranscriptional modification, plays vital role modulating stability, activity localization of modified proteins enzymatic cascade. This review was motivated by accumulating evidence series E3 ligases deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors key enzymes to govern functions almost all components TME. In this review, we systematically summarize substrate involved formation TME DUBs recognize these proteins. addition, several promising techniques targeted protein degradation hijacking intracellular ubiquitin-ligase machinery are introduced.

Language: Английский

Citations

14
Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro DOI Creative Commons
Yuanqin Du,

Bin Yuan,

Yi-Xian Ye

et al.

Journal of Hepatocellular Carcinoma, Journal Year: 2024, Volume and Issue: Volume 11, P. 565 - 580

Published: March 1, 2024

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed investigate effect PL on tumor growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, vivo models EMT HCC-associated lung metastasis developed through tail vein situ injections In imaging hematoxylin eosin staining used evaluate HCC modeling metastasis. After intervention, expression levels Snail, vimentin, E-cadherin, N-cadherin liver evaluated immunohistochemistry Western blot. An vitro TGF-β-induced cell model was detect mRNA a polymerase chain reaction. Their protein detected by immunofluorescence Results: experiments demonstrated that significantly reduced N-cadherin, while increasing E-cadherin at levels, effectively inhibiting confirmed up-regulated epithelial markers, down-regulated mesenchymal inhibited Conclusion: inhibits Snail expression, up-regulates down-regulates vimentin preventing reducing Keywords: plumbagin, carcinoma, transition, pulmonary metastasis,

Language: Английский

Citations

4
Biomarkers for the detection of circulating tumor cells DOI
Karol Gostomczyk,

Magdalena Drozd,

Mohammed Dheyaa Marsool Marsool

et al.

Experimental Cell Research, Journal Year: 2025, Volume and Issue: 448(1), P. 114555 - 114555

Published: April 12, 2025

Language: Английский

Citations

0