Dissecting the dual role of OTU family proteins in tumor progression and immune escape DOI Creative Commons

Xiaolong Tang,

Yadan Li, Yongshuo Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 21, 2025

As a core mechanism regulating intracellular protein homeostasis, the dynamic equilibrium between ubiquitination and deubiquitination profoundly impacts functionality fate of target proteins. The Ovarian tumor domain (OTU) family, vital subclass deubiquitinating enzymes, comprises 16 members that mediate ubiquitin binding hydrolysis through their characteristic OTU domain. Recent years have witnessed growing interest in family oncology immunology research. This review comprehensively elucidates mechanisms by which regulate tumor-associated signaling networks via substrate-specific deubiquitination. On one hand, they directly govern cell proliferation, metastasis, apoptosis modulating stability key substrates. other orchestrate progression regulation inflammatory intensity, immune response duration, evasion within microenvironment (TME), thereby constructing multidimensional regulatory network development. These findings not only unveil pivotal role tumorigenesis modulation but also establish theoretical foundation for developing novel anti-tumor therapeutics targeting processes. Notably, OTUs emerge as high-potential therapeutic targets with high translational relevance refining precision-guided tumor-immunotherapy integration strategies.

Язык: Английский

Ultrasound-responsive Engineered Bacteria mediated Specific Controlled Expression of Catalase and Efficient Radiotherapy DOI Creative Commons

Zichao Liu,

Lingling Lei,

Zenan Zhang

и другие.

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101620 - 101620

Опубликована: Фев. 27, 2025

The limited efficacy of radiotherapy (RT) in breast cancer is intricately linked to the hypoxic tumor microenvironment. Delivering catalase (CAT) decompose hydrogen peroxide (H2O2) into oxygen a promising strategy address this. However, challenges such as low transport efficiency, accumulation normal organs, and lack spatiotemporal control hinder its clinical application. To this, we developed an innovative ultrasound-responsive engineered bacteria-based CAT delivery system (UEB), which effectively overcomes these by targeting tumors, ensuring efficient expression, providing precise over H2O2 decomposition. When subjected ultrasound irradiation, decomposition production UEB increased threefold, demonstrating excellent capability alleviating hypoxia. organs was minimized through this strategy. Moreover, bacteria enhance reactive species (ROS) generation, improving RT outcomes significantly inhibiting growth, resulting 10-fold size reduction. This study demonstrates for specific, controlled expression application radiotherapy.

Язык: Английский

Процитировано

1
Integrative analysis of single-cell and bulk RNA sequencing reveals the oncogenic role of ANXA5 in gastric cancer and its association with drug resistance DOI Creative Commons

Denggang Chen,

Peng Zhang,

Li Gong

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

Background Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements chemotherapy, surgery, targeted therapies, delayed diagnosis due to overlooked early symptoms leads poor prognosis. Methods We integrated bulk RNA sequencing single-cell datasets from TCGA, GEO, OMIX001073, employing normalization, batch effect correction, dimensionality reduction methods identify key cell populations associated GC invasion epithelial-mesenchymal transition (EMT), as well analyze the tumor immune microenvironment. Results Our analysis identified MUC5AC+ malignant epithelial cluster significant player EMT. Cluster 1, representing this population, exhibited higher EMT scores compared other clusters. Survival showed that high abundance 0 correlated improved survival rates (P=0.012), whereas 1 was poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 GABARAPL2 two critical genes upregulated tumors. High-risk patients demonstrated increased infiltration worse prognosic. Analysis mutation burden (TMB) indicated low TMB high-risk group had worst Wet-lab validation experiments confirmed oncogenic role ANXA5, showing its facilitation proliferation, invasion, migration while suppressing apoptosis. Conclusion This study offers novel insights into subpopulations cells their roles progression. It provides potential therapeutic targets combat GC, contributing crucial understanding fundamental mechanisms drug resistance gastrointestinal cancers.

Язык: Английский

Процитировано

0
Therapeutic strategies for adrenocortical carcinoma: integrating genomic insights, molecular targeting, and immunotherapy DOI Creative Commons
Jing Sun, Jiaxuan Huai, Wenhui Zhang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 12, 2025

Adrenocortical carcinoma (ACC) is an uncommon and highly aggressive cancer originating in the adrenal cortex, characterized by a high likelihood of recurrence unfavorable survival rates, particularly advanced disease stages. This review discusses complex molecular pathogenesis ACC, focusing on critical pathways implicated tumorigenesis providing potential targets for therapy: Wnt/β-catenin signaling pathway, IGF2/IGF1R axis, apoptosis pathway regulated p53. Current treatment strategies include surgical resection mitotane, sole adrenolytic agent approved FDA; however, its effects are suboptimal. Cytotoxic chemotherapy combined with mitotane may be applied, but benefits limited so far. In following review, we outline emerging targeted therapies, such as mTOR inhibitors tyrosine kinase (TKIs), which show favorable preclinical clinical data, especially treatment-resistant ACC. We also emphasize possible role immune checkpoint (ICIs) management although their effectiveness still under study. Upcoming trends involve forms personalized medicine, where profiling integrated to identify actionable biomarkers administered therapies. will attempt provide comprehensive framework how recent breakthroughs genomics coupled advances therapies immunotherapy, can improve management.

Язык: Английский

Процитировано

0
Exploration of SUSD3 in pan-cancer: studying its role, predictive analysis, and biological significance in various malignant tumors in humans DOI Creative Commons
Fei Zhong,

Shining Mao,

Shu‐Fen Peng

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Background The SUSD3 protein, marked by the Sushi domain, plays a key role in cancer progression, with its expression linked to tumor advancement and patient prognosis. Altered levels could serve as predictive biomarker for progression. Recognized novel susceptibility marker, presents promising target antibody-based therapies, offering potential approach prevention, diagnosis, treatment of breast cancer. Methods Using HPA GeneMANIA platforms, distribution protein across tissues was analyzed, while healthy were compared using Cancer Genome Atlas data. TISCH STOmics DB databases facilitated mapping different cell types spatial relationship markers. Univariate Cox regression assessed prognostic significance various cancers. Genomic alterations explored through cBioPortal database. predictor immunotherapy response investigated TIMER2.0, GSEA/GSVA identified related biological pathways. Drugs targeting CellMiner, CTRP, GDSC databases, complemented molecular docking studies. In vitro experiments demonstrated that knockdown lines significantly reduced proliferation migration. Results variations pan-cancer cohorts are closely prognosis malignancies. microenvironment (TME), is predominantly expressed monocytes/macrophages CD4+ T cells. Research indicates strong correlation between biomarkers, immune infiltration, immunomodulatory factors. To explore regulatory role, StromalScore, ImmuneScore, ESTIMATE, Immune Infiltration metrics employed. Molecular studies revealed selumetinib inhibits proliferation. Finally, Conclusion These findings provide valuable insights establish foundation further exploration SUSD3’s pan-carcinomas. Additionally, they offer perspectives targets development innovative therapeutic strategies treatment.

Язык: Английский

Процитировано

0
Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle DOI Creative Commons
Mengran Qin, Yizhen Wang,

Zihan Wang

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 10, 2025

This study investigates how miR-146a-5p, found in adipose tissue-derived small extracellular vesicles (sEV), influences mitochondrial autophagy and its impact on delaying skeletal muscle aging through the targeting of Fbx32. The findings highlight miR-146a-5p as crucial development aging, influencing autophagy, apoptosis, differentiation, proliferation, collectively impacting atrophy. In C2C12 cells, mimics decreased reactive oxygen species (ROS) levels, while enhancing ATP production; conversely, inhibitors had opposite effects. Furthermore, miR-146a-5p-enriched sEV from tissue alleviated atrophy aged mice promoted fiber growth repair by regulating apoptosis. Mechanistically, modulated myoblasts Fbx32 FoxO3 signaling pathway. led to a notable decrease apoptosis-related gene expression, reduced ROS production, elevated levels. conclusion, derived WAT-sEV modulates myoblast ROS, differentiation Fbx32/FoxO3 axis. work presents novel molecular target theoretical framework for developing therapies muscle-related disorders.

Язык: Английский

Процитировано

0
Epigenetic modifications in breast cancer: from immune escape mechanisms to therapeutic target discovery DOI Creative Commons
Zhihua Kang, Junlin Wang, Jiyan Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 17, 2025

Breast cancer (BC) is one of the most prevalent malignant tumors among women globally, with number cases accounting for even more than 1/3 all tumor patients in women. Recent studies have found that incidence BC increasing every year. Despite great progress made treatment, characteristics cells, such as strong immune evasion, easy recurrence and drug resistance, are still main reasons limiting survival patients. Epigenetics becoming an important method to reveal development cancer, mainly through study DNA methylation, histone modification, chromatin structure changes non-coding RNA. In addition, researchers epigenetic markers potential early detection personalized treatment BC. Inhibitors targeting epigenetically modified enzymes effective treating a wide range provide significant patient quality life. Therefore, this review will comprehensively summarize role modifications development. Second, paper focus on summarizing how induce formation microenvironment (TIME) Targeting mechanism action provides new perspectives unravel complex process development, while paving way novel diagnostic therapeutic targets. future, by integrating multi-omics data enable deeper understanding pathogenesis BC, we be able promote overall precision medicine.

Язык: Английский

Процитировано

0
GPX2 inhibition enhances antitumor efficacy of lenvatinib via promoting immunogenic cell death in hepatocellular carcinoma DOI Creative Commons

Yingzheng Tan,

Lei Yang, Tao Xu

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 18, 2025

Immunogenic cell death (ICD) is a distinct subtype of regulatory death, and represents potential mechanism to remodel the tumor microenvironment. Lenvatinib established as first-line therapy for advanced hepatocellular carcinoma (HCC), but drug resistance limits its efficiency. Our previous research showed that lenvatinib can inhibit GPX2 expression induce reactive oxygen species (ROS)-related apoptosis in HCC. The present study intends explore whether ICD clarify underlying mechanisms Flow cytometry was utilized detect levels CRT CD markers, measure intracellular ROS levels, assess apoptosis. Western blot analysis employed determine changes protein while qRT-PCR used quantify alterations mRNA levels. Subcutaneous allograft models were investigate against Immunohistochemical (IF) staining ratio CD8+GZMB+ cells. Herein, we found HCC cells treated with or si-GPX2 increased such exposure, ATP secretion, HMGB1 release. Notably, demonstrated promoted dendritic (DCs) maturation CD8+ T activation, thus inducing when co-cultured peripheral blood mononuclear Additionally, further inhibition triggers endoplasmic reticulum stress (ERS) cells, which mediated by accumulation ROS. findings indicate pre-treatment antioxidant N-acetylcysteine suppressed lenvatinib-induced on membrane, secretion release, inhibited Furthermore, also ERS inhibitor ISRIB could reverse upregulation biomarkers. Moreover, identified downregulation enhanced efficacy via triggering ERS-mediated This uncovered be potent inducer, trigger increasing valuable insights into Collectively, our highlight significant therapeutic combination targeting treatment

Язык: Английский

Процитировано

0
Ultrasound-responsive release of CD39 inhibitor overcomes adenosine-mediated immunosuppression in triple-negative breast cancer DOI
Yijie Chen,

Yue Song,

Chao Zhang

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер 383, С. 113819 - 113819

Опубликована: Май 8, 2025

Язык: Английский

Процитировано

0
Emerging tumor hypoxia-relieving nanotherapeutics for boosting photodynamic therapy DOI
Fujun Yang, Fei Chen,

Shumeng Li

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер 516, С. 163962 - 163962

Опубликована: Май 20, 2025

Язык: Английский

Процитировано

0
Dissecting the dual role of OTU family proteins in tumor progression and immune escape DOI Creative Commons

Xiaolong Tang,

Yadan Li, Yongshuo Liu

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 21, 2025

As a core mechanism regulating intracellular protein homeostasis, the dynamic equilibrium between ubiquitination and deubiquitination profoundly impacts functionality fate of target proteins. The Ovarian tumor domain (OTU) family, vital subclass deubiquitinating enzymes, comprises 16 members that mediate ubiquitin binding hydrolysis through their characteristic OTU domain. Recent years have witnessed growing interest in family oncology immunology research. This review comprehensively elucidates mechanisms by which regulate tumor-associated signaling networks via substrate-specific deubiquitination. On one hand, they directly govern cell proliferation, metastasis, apoptosis modulating stability key substrates. other orchestrate progression regulation inflammatory intensity, immune response duration, evasion within microenvironment (TME), thereby constructing multidimensional regulatory network development. These findings not only unveil pivotal role tumorigenesis modulation but also establish theoretical foundation for developing novel anti-tumor therapeutics targeting processes. Notably, OTUs emerge as high-potential therapeutic targets with high translational relevance refining precision-guided tumor-immunotherapy integration strategies.

Язык: Английский

Процитировано

0