LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer DOI Creative Commons
Miaomiao Pei, Jieming Zhang, Zhentao Yu

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 12, 2024

Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, effect LINC02139 its mechanism on gastric cancer (GC) is still unknown. We revealed upregulated GC cell lines tissues high expression was correlated with advancement patients. Functionally, overexpression promoted, while knockdown impaired proliferation, migration, invasion vitro impeded tumorigenesis a tumor xenograft model vivo. Mechanistically, directly bound to XIAP increased protein level by maintaining stability through inhibition ubiquitination proteasome-dependent degradation pathway. Importantly, regulatory function LINC02139-mediated oncogenic effects demonstrated. Both vivo experiments collaboratively modulate growth apoptosis. Analysis clinical further confirmed upregulation positive association between expression. These findings established as driver highlighted crucial involvement LINC02139-XIAP axis progression, suggesting potential promising therapeutic target for combating advancement.

Language: Английский

USP3 plays a critical role in the induction of innate immune tolerance DOI Creative Commons
Tianhao Duan, Yanchun Feng, Yang Du

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(12)

Published: Nov. 16, 2023

Abstract Microbial products, such as lipopolysaccharide (LPS), can elicit efficient innate immune responses against invading pathogens. However, priming with LPS induce a form of memory, termed “tolerance”, which blunts subsequent NF‐κB signaling. Although epigenetic and transcriptional reprogramming has been shown to play role in the involvement post‐translational regulation remains unclear. Here, we report that ubiquitin‐specific protease 3 (USP3) participates establishing “tolerance” memory through non‐transcriptional feedback. Upon signaling activation, USP3 is stabilized exits nucleus. The cytoplasmic specifically removes K63‐linked polyubiquitin chains on MyD88, thus negatively regulating TLR/IL1β‐induced inflammatory activation. Importantly, translocation prerequisite step for deubiquitinate MyD88. Additionally, could retention faster stronger USP3, enabling it quickly shut down upon second challenge. This work identifies previously unrecognized feedback loop MyD88–USP3 axis, critical inducing normal memory.

Language: Английский

Citations

6

The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis DOI Creative Commons
Feng Zhang, Xiaolei Chen, Hongfang Wang

et al.

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 19, 2024

Abstract Background Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct risk model and evaluate prognostic value of ubiquitination-related genes in MM. Methods results The data on MM samples were downloaded from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. consistent cluster ESTIMATE algorithm create distinct clusters. constructed through single-factor multiple-factor analysis. ROC curve plotted compare survival difference between high- low-risk groups. nomogram validate predictive capability model. A total 87 obtained, with 47 showing high expression group. According analysis, 4 clusters determined. immune infiltration, survival, prognosis differed significantly among tumor purity higher 1 3 than 2 4, while score stromal lower 3. proportion B cells memory, plasma cells, T CD4 naïve lowest 4. KLHL24, HERC6, USP3, TNIP1, CISH highly expressed high-risk AICAr BMS.754,807 exhibited drug sensitivity group, whereas Bleomycin showed demonstrated good efficacy predicting patients using TCGA GEO datasets. Conclusions by can be effectively predict patients. warrant further investigation as therapeutic targets combat resistance.

Language: Английский

Citations

2

Ubiquitin specific peptidase 3: an emerging deubiquitinase that regulates physiology and diseases DOI Creative Commons
Yizhu Wang,

Yanlong Shi,

Kaiyi Niu

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 21, 2024

Abstract Proteins are the keystone for execution of various life activities, and maintenance protein normalization is crucial organisms. Ubiquitination, as a post-transcriptional modification, widely present in organisms, it relies on sophisticated ubiquitin-proteasome (UPS) system that controls quality modulates lifespan. Deubiquitinases (DUBs) counteract ubiquitination essential homeostasis. Ubiquitin specific peptidase 3 (USP3) member DUBs has received increasing attention recent years. USP3 novel chromatin modifier tightly regulates DNA damage response (DDR) maintains genome integrity. Meanwhile, acts key regulator inflammatory vesicles sustains normal operation innate immune system. In addition, aberrantly expressed wide range cancers, such gastric cancer, glioblastoma neuroblastoma, implicating could be an effective target targeted therapies. this review, we retrace all current researches USP3, describe structure elucidate its functions damage, responses cell cycle, summarize important role multiple cancers diseases.

Language: Английский

Citations

1

circRNA6448-14/miR-455-3p/OTUB2 axis stimulates glycolysis and stemness of esophageal squamous cell carcinoma DOI Creative Commons
Yaowen Zhang, Heming Zhang, Chenyu Wang

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(11), P. 9485 - 9497

Published: May 30, 2024

Background: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with high incidence. This study aimed to reveal the complete circRNA-miRNA-mRNA regulatory network in ESCC and validate its function mechanism. Method: Expression of OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 2 (OTUB2) was analyzed by bioinformatics find binding sites between circRNA6448-14 miR-455-3p, as well miR-455-3p OTUB2. The relationships were verified RNA Immunoprecipitation (RIP) dual-luciferase assay. expressions circRNA6448-14, OTUB2 detected quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay measured viability, spheroid formation assessed ability stem sphere formation. Western blot (WB) determined expression marker proteins surface rate-limiting enzyme glycolysis. Seahorse XFe96 extracellular flux analyzer rate acidification cellular oxygen consumption. Corresponding kits glucose consumption, lactate production, adenosine triphosphate (ATP) generation. Results: In ESCC, highly expressed contrast miR-455-3p. Knocking down could prevent glycolysis stemness cells. Additionally, enhanced sponging Overexpression or silencing reversed inhibitory effect knockdown on stemness. Conclusion: research demonstrated that circRNA6448-14/miR-455-3p/OTUB2 axis induced Our revealed novel which may serve potential therapeutic target for ESCC.

Language: Английский

Citations

1

LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer DOI Creative Commons
Miaomiao Pei, Jieming Zhang, Zhentao Yu

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 12, 2024

Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, effect LINC02139 its mechanism on gastric cancer (GC) is still unknown. We revealed upregulated GC cell lines tissues high expression was correlated with advancement patients. Functionally, overexpression promoted, while knockdown impaired proliferation, migration, invasion vitro impeded tumorigenesis a tumor xenograft model vivo. Mechanistically, directly bound to XIAP increased protein level by maintaining stability through inhibition ubiquitination proteasome-dependent degradation pathway. Importantly, regulatory function LINC02139-mediated oncogenic effects demonstrated. Both vivo experiments collaboratively modulate growth apoptosis. Analysis clinical further confirmed upregulation positive association between expression. These findings established as driver highlighted crucial involvement LINC02139-XIAP axis progression, suggesting potential promising therapeutic target for combating advancement.

Language: Английский

Citations

1