Gene最新文献

{"title":"Small extracellular vesicles carrying miRNA34 in Alzheimer’s disease: effects on oxidative stress, neuroinflammation, cognitive function, and mitochondrial/ferroptosis-related protein regulation","authors":"Hamit Çelik ,&nbsp;Oğuz Çelik ,&nbsp;Şeyma Aydın ,&nbsp;Sefa Küçükler ,&nbsp;Selim Çomaklı ,&nbsp;Ahmet Topal ,&nbsp;Ramazan Akay ,&nbsp;Sinan Gönüllü ,&nbsp;Mustafa Onur Yıldız ,&nbsp;Bülent Alım ,&nbsp;Selçuk Özdemir","doi":"10.1016/j.gene.2026.150014","DOIUrl":"10.1016/j.gene.2026.150014","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, oxidative stress, and persistent neuroinflammation. Recent studies have increasingly focused on the regulatory role of microRNAs in AD pathogenesis. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEV) enriched with microRNA34 (miRNA34) to target key pathogenic mechanisms of AD. We hypothesized that miRNA34-loaded sEV could alleviate oxidative damage, inhibit neuroinflammatory responses and ferroptosis, reduce mitochondrial impairment, and ultimately improve cognitive function. We evaluated the effects of miRNA34 administration on oxidative stress markers, pro-inflammatory cytokines, synaptic plasticity indicators, and behavioral outcomes in an <em>in vivo</em> Aβ-induced mouse model of AD. The experimental design included five groups, each consisting of seven mice. The findings demonstrated that miRNA34-loaded sEV treatment significantly reduced oxidative stress and neuroinflammation while enhancing memory and learning performance. Overall, our results indicate that miRNA34-enriched sEV represent a promising and minimally invasive therapeutic strategy capable of modulating AD pathogenesis. This research provides a novel perspective on the potential clinical application of miRNA34 and sEVin neurodegenerative disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150014"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel frameshift variant in PURA syndrome: role of NMD pathway in disease mechanism","authors":"Huiqin Yang,&nbsp;Xihui Zhou","doi":"10.1016/j.gene.2025.149930","DOIUrl":"10.1016/j.gene.2025.149930","url":null,"abstract":"<div><h3>Background</h3><div>PURA syndrome is a rare genetic disorder characterized by obvious hypotonia, feeding difficulties, apnea, and drowsiness, which is caused by variants in the <em>Purine Rich Element Binding Protein A (PURA)</em> on chromosome 5q31.2-q31.3, and is inherited in an autosomal dominant manner. This condition presents challenges for early diagnosis and effective treatment. This study investigates its pathogenic mechanisms and potential therapeutic strategies.</div></div><div><h3>Methods</h3><div>Peripheral blood samples were collected from a Chinese newborn with severe hypotonia and his parents. Whole-exome sequencing (WES) and Sanger validation identified a novel <em>PURA</em> variant, which had not been previously reported. To explore the potential involvement of nonsense-mediated mRNA decay (NMD) in PURA syndrome, wild-type (WT) and variant (Var) <em>PURA</em> expression vectors were constructed and transiently transfected into 293 T cells via liposomal transfection. Real-time quantitative polymerase chain reaction (PCR) and Western blotting were performed to analyze the <em>PURA</em> expression. The levels of <em>PURA</em> mRNA and protein were assessed following treatment with the NMD inhibitor cycloheximide (CHX) and the small interfering RNA targeting Up-frameshift protein 1 (siRNA-UPF1), a key NMD factor.</div></div><div><h3>Results</h3><div>The WES identified a novel heterozygous frameshift variant in exon 1 of PURA (NM_005859.5): c.632_651dup; p.(Leu218Trpfs*14), which introduces a premature termination codon (PTC). However, no such variant was detected in his parents. Functional validation assays revealed that the variant construct expressed significantly lower levels of <em>PURA</em> mRNA and protein compared to the WT. CHX treatment and siRNA-UPF1 transfection significantly increased the mRNA and protein expression levels of <em>PURA</em> in the variant construct.</div></div><div><h3>Conclusion</h3><div>The novel PURA variant, c.632_651dup; p.(Leu218Trpfs*14), is a pathogenic heterozygous frameshift. The NMD pathway is involved in the degradation of its aberrant transcript. Our research expands the genotypic spectrum of pathogenic <em>PURA</em> variants, and offers a new perspective for potential therapeutic intervention.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149930"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity and genome-wide association mapping for salt stress tolerance in diverse parental lines of hybrid rice","authors":"Md. Ruhul Quddus ,&nbsp;M. Akhlasur Rahman ,&nbsp;Mehfuz Hasan ,&nbsp;Md. Golam Rasul ,&nbsp;Md. Abdul Mannan ,&nbsp;Md. Jamil Hasan","doi":"10.1016/j.gene.2026.150003","DOIUrl":"10.1016/j.gene.2026.150003","url":null,"abstract":"<div><div>Salinity, exacerbated by climate change, is a major threat to rice production. Seedling biomass under salt stress is one of the key indicators of salinity tolerance. This is the first study that involved 276 diverse hybrid rice parental lines to analyze GWAS on critical trait seedling biomass under 12 dS/m salt stress. Genetic diversity analysis using UPGMA clustering separated the genotypes into three major and three small distinct groups. Path analysis among 25 traits revealed that root biomass was important determinant for maintaining seedling biomass under salt stress. Genome-wide association analysis (GWAS) for seedling biomass traits under salt stress detected seven significant SNP markers on chromosomes 2, 4, 6, 7, 10, and 11. We report three novel candidate genes associated with seedling biomass maintenance under salt stress: <em>LOC_Os02g55630.1</em> (chloroplast activity), <em>LOC_Os07g04240.1</em> (mitochondrial function), and the uncharacterized <em>LOC_Os04g06520.1</em>. In conclusion, a robust root system is vital for seedling biomass retention under salt stress, and identified genetic markers will be useful for the development of salt-resilient hybrid and inbred rice.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 150003"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The R2R3-MYB transcription factor GhMYB35 governs anther development and pollen viability in upland cotton","authors":"Qiyue Ma ,&nbsp;Ningna Wang ,&nbsp;Kaikai Qiao ,&nbsp;Kun Luo ,&nbsp;Chenglong Zhao ,&nbsp;Jiaxuan Yan ,&nbsp;Shuli Fan ,&nbsp;Junkang Rong ,&nbsp;Qifeng Ma","doi":"10.1016/j.gene.2025.149990","DOIUrl":"10.1016/j.gene.2025.149990","url":null,"abstract":"<div><div>Male reproductive development is fundamental to the life cycle of flowering plants, culminating in seed production. Aberrations in anther development frequently lead to male sterility, yet the underlying molecular mechanisms in upland cotton (<em>Gossypium hirsutum</em>) remain largely uncharacterized. The R2R3-MYB family of transcription factors are known key regulators of diverse developmental processes, including male fertility in several model species. Here, we identify and functionally characterize <em>GhMYB35</em>, an R2R3-MYB transcription factor that plays an essential role in cotton anther development. CRISPR/Cas9-mediated knockout of <em>GhMYB35</em> resulted in complete male sterility, with mutants (<em>ghmyb35</em>) exhibiting indehiscent anthers, shorter filaments, and a total absence of viable pollen. Expression analyses reveal that <em>GhMYB35</em> is predominantly expressed in anthers, with peak expression of its A- and D-subgenome homoeologs occurring at developmental stage 7. Subcellular localization results show that both<!--> <em>GhMYB35_A</em> <!-->and<!--> <em>GhMYB35_D</em> <!-->are nuclear-localized transcription factors. Furthermore, the total absence of GhMYB35 leads to pollen abortion and subsequent anther collapse without dehiscence. Collectively, our findings establish <em>GhMYB35</em> as a critical regulator of anther maturation, thereby elucidating a key component of the molecular network governing male fertility in cotton.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149990"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational epitope discovery and in silico design of a bispecific antibody model (COMED hook) to block Plasmodium invasion into erythrocytes","authors":"Ahmet Efe Köseoğlu ,&nbsp;Nadir Gül ,&nbsp;Tuğçe Duran ,&nbsp;Cenk Öztürk ,&nbsp;Nezih Hekim","doi":"10.1016/j.gene.2026.149999","DOIUrl":"10.1016/j.gene.2026.149999","url":null,"abstract":"<div><div>Malaria remains a major global health threat, with <em>Plasmodium</em> species, especially <em>P. falciparum</em>, increasingly resistant to drugs and vaccines. Novel strategies are needed to address antigenic diversity and the parasite’s intracellular immune evasion. This study aimed to identify conserved and immunogenic B-cell epitopes in <em>P. falciparum</em> and human erythrocytes to design a bispecific antibody model, COMED hook, capable of blocking erythrocyte invasion. Surface and secretory proteins of <em>P. falciparum</em> and erythrocytes were retrieved from public databases. B-cell epitopes were predicted and filtered based on antigenicity, allergenicity, and toxicity. Conservancy was assessed via BLAST. Selected epitopes were structurally modeled, docked to B-cell receptors, and used for antibody design via DiffAb. A total of 123 antigenic <em>P. falciparum</em> B-cell epitopes were identified, with 58 conserved across species. Additionally, 92 non-conserved human erythrocyte B-cell epitopes were discovered, of which 12 were selected as host-targeting domains. Two highly conserved <em>Plasmodium</em> epitopes (KHVETWTQRVQNM, LHSNFYIKRF) were predicted to have favorable Fab binding. Designed antibodies likewise exhibited computationally suggested sequence and docking profiles compatible with COMED hook construction. Overall, this study presents an <em>in silico</em> computational design framework for a bispecific antibody model targeting both <em>Plasmodium</em> and host erythrocytes, generating testable predictions for future work. The predicted interactions and the proposed COMED hook concept will require experimental validation to assess biological feasibility.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149999"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the winding road toward precision prostate cancer care","authors":"Syed Rahman ,&nbsp;Adith S. Arun ,&nbsp;Isaac Yi Kim ,&nbsp;William K. Oh ,&nbsp;Joseph W. Kim ,&nbsp;William J. Kim","doi":"10.1016/j.gene.2025.149966","DOIUrl":"10.1016/j.gene.2025.149966","url":null,"abstract":"<div><div>Prostate cancer (PCa) remains the second leading cause of cancer-related mortality among U.S. men, driven in large part by metastatic castration-resistant prostate cancer (mCRPC) despite initial responses to androgen-receptor (AR)–targeted therapies. Over the last two decades, treatment options for mCRPC have significantly expanded to include novel therapeutic modalities that integrate biomarker-guided patient selection. These biomarker-driven therapies have ushered us into the era of “precision oncology” in prostate cancer care, and we highlight key developments. In light of these promising early results, we also review key opportunities and challenges ahead. Additionally, we share a conceptual roadmap to leverage multi-omics molecular data in the era of Artificial Intelligence/Machine Learning (AI/ML) to accelerate progress in prostate cancer precision medicine. Specifically, we discuss how these tools may help facilitate the development of near-patient preclinical models for prostate cancer to better capture key aspects of prostate cancer tumor biology. We also discuss a potential path toward accelerating translation of laboratory discoveries into clinical practice for PCa patients.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149966"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence for the LRRK2 p.L1795F variant in a Southern Italian cohort with Parkinson’s disease","authors":"Monica Gagliardi ,&nbsp;Radha Procopio ,&nbsp;Alessia Felicetti ,&nbsp;Andrea Quattrone ,&nbsp;Gennarina Arabia ,&nbsp;Maurizio Morelli ,&nbsp;Antonio Gambardella ,&nbsp;Grazia Annesi ,&nbsp;Aldo Quattrone","doi":"10.1016/j.gene.2026.150001","DOIUrl":"10.1016/j.gene.2026.150001","url":null,"abstract":"<div><h3>Background</h3><div>Pathogenic variants in the <em>LRRK2</em> gene are among the most common genetic causes of autosomal dominant Parkinson’s disease (PD). A recent study provided strong genetic and functional evidence supporting the pathogenicity of the rare missense variant p.L1795F (c.5385G &gt; T), identified exclusively in individuals of European ancestry. However, its prevalence in Southern European populations remains unknown.</div></div><div><h3>Objective</h3><div>The aim of the study was to evaluate the frequency of the p.L1795F variant in a cohort of PD patients from Southern Italy.</div></div><div><h3>Methods</h3><div>We screened 300 unrelated PD patients using Sanger sequencing to detect the presence of the p.L1795F (c.5385G &gt; T) variant in the <em>LRRK2</em> gene.</div></div><div><h3>Results</h3><div>No carriers of the p.L1795F variant were identified in our Southern Italian cohort.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the p.L1795F variant may have very low or undetectable frequency in the Southern Italian population. Our results highlight the importance of including underrepresented geographic regions in genetic screening efforts for PD to better understand the population-specific distribution of pathogenic variants.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 150001"},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the dual mechanisms of Wuwei Wentong Chubi Capsule in alleviating rheumatoid arthritis: synergistic anti-inflammatory and anti-coagulant effects","authors":"Fanfan Wang ,&nbsp;Jian Liu ,&nbsp;Yanyan Fang ,&nbsp;Yang Li ,&nbsp;Xueni Cheng ,&nbsp;Shengfeng Liu","doi":"10.1016/j.gene.2025.149991","DOIUrl":"10.1016/j.gene.2025.149991","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and multi-organ damage. While existing therapies alleviate symptoms, they are accompanied by significant adverse effects. Fibroblast-like synoviocytes (FLS) drive RA progression through inflammation-coagulation interactions, necessitating safer multitarget drugs. Jianpi Wenyang Tongluo Prescription-Wuwei Wentong Chubi Capsule (WWT), a traditional Chinese medicine formula targeting the “cold-dampness obstruction syndrome” in RA, has demonstrated clinical efficacy, yet its mechanism remains unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate the therapeutic effects of WWT on adjuvant-induced arthritis (AA) rats with cold-dampness syndrome and explore its underlying mechanisms in regulating inflammation-coagulation balance and organ protection.</div></div><div><h3>Materials and methods</h3><div>AA rats with cold-dampness syndrome were established using Freund’s complete adjuvant (FCA) and a climate chamber, and treated with WWT (low/medium/high doses). Synovial pathology, organ function, inflammatory, and coagulation parameters were evaluated. Molecular docking, protein–protein interaction (PPI) networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were employed to identify key targets, with Western blot (WB) and immunofluorescence used to validate JAK2/STAT3 pathway activation. A coculture model of peripheral blood mononuclear cells (PBMCs) and FLS from RA patients was constructed for in vitro validation.</div></div><div><h3>Results</h3><div>In AA rats, WWT dose-dependently decreased pro-inflammatory cytokines (IL-6, IL-17) and pro-coagulant factors (PAF, FDP), while increasing anti-inflammatory cytokine IL-10 and anticoagulant factor PGI2 (P &lt; 0.01). WWT reversed synovial mitochondrial vacuolation and protected liver and kidney function. Bioinformatics analysis and molecular docking revealed JAK2/STAT3 as the core target, with wogonin and icariin stably binding to JAK2 (ΔG = -8.2/-7.7 kcal/mol) and STAT3 (ΔG = -7.9/-9.9 kcal/mol). WWT rescued inflammation and hypercoagulation induced by the JAK2/STAT3 activator coumermycin A1. In vitro, WWT-containing serum inhibited the proliferation of cocultured RA-PBMCs and FLS and the secretion of pro-inflammatory and pro-coagulant factors by blocking JAK2/STAT3 and STAT3 nuclear translocation.</div></div><div><h3>Conclusions</h3><div>WWT alleviates RA progression by restoring inflammation-coagulation balance and protecting multi-organ function through inhibition of the JAK2/STAT3 pathway. This study integrates traditional Chinese medicine theory with molecular pathological mechanisms, providing a scientific basis for WWT as a multitarget therapeutic for RA.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149991"},"PeriodicalIF":2.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SR protein kinase FoSrk1 integrates RNA splicing, carbon metabolism, and virulence in Fusarium oxysporum f. sp. cubense","authors":"Han Ouyang ,&nbsp;Jiayi Peng ,&nbsp;Zhouqi Huang ,&nbsp;Yicong Huang ,&nbsp;Yinglan Wen ,&nbsp;Yuan Xu ,&nbsp;Yu Long ,&nbsp;Huijiao Lin ,&nbsp;Qiyan Fu ,&nbsp;Zhaojian Ding","doi":"10.1016/j.gene.2025.149954","DOIUrl":"10.1016/j.gene.2025.149954","url":null,"abstract":"<div><div><em>Fusarium oxysporum</em> f. sp. <em>cubense</em> (Foc), the causal agent of banana Fusarium wilt, is one of the most destructive plant pathogens worldwide. However, the molecular mechanisms that integrate fungal growth, metabolism, and virulence remain poorly understood. This study identifies and functionally characterizes FoSrk1, a serine/arginine-rich protein kinase (SRPK), in Foc. Deletion of <em>FoSrk1</em> markedly impaired vegetative growth, reduced aerial mycelium formation and conidiation, and significantly attenuated virulence toward banana plantlets. The mutant also exhibited compromised utilization of diverse carbon sources, accompanied by altered expression of 32 genes involved in carbon metabolism. Complementation with the wild-type <em>FoSrk1</em> allele restored normal growth and pathogenicity, confirming the gene’s essential role. Transcriptomic analyses revealed that loss of <em>FoSrk1</em> altered the expression of 2,500 genes and was associated with changes in 37 alternative splicing events, predominantly intron retention, affecting transcripts linked to protein metabolism, ribosome biogenesis, and redox processes. Moreover, several virulence-associated genes encoding ABC transporters, cytochrome P450 enzymes, and hydrophobins were downregulated in the <em>FoSrk1</em>-deficient strain. These findings suggest that FoSrk1 acts as an important regulator that couples RNA processing with metabolic and pathogenic pathways and is required for normal fungal development and virulence. This study provides new insight into the molecular basis of pathogenic adaptation and identifies FoSrk1 as a potential target for antifungal intervention strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149954"},"PeriodicalIF":2.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinating enzymes in endometrial cancer and cervical cancer","authors":"Chenlu Tang,&nbsp;Xiaofeng Jin","doi":"10.1016/j.gene.2025.149988","DOIUrl":"10.1016/j.gene.2025.149988","url":null,"abstract":"<div><div>Endometrial cancer (EC) is one of the three most common malignancies of the female reproductive system, with its global incidence and disease-related mortality continuing to rise. Cervical cancer (CC), also known as uterine cervical cancer, refers to cancer occurring in the cervix. Despite the development of various therapeutic strategies, patient prognosis and survival rates remain poor due to high rates of metastasis and recurrence. Ubiquitination denotes the process by which ubiquitin is covalently attached to target proteins, while deubiquitinases (DUBs) catalyze the reverse process. Accumulating evidence indicates that dysregulation of deubiquitination plays significant roles in the pathogenesis and progression of both EC and CC. This review systematically summarizes recent research advances in DUBs, outlining their intrinsic characteristics, classification, catalytic mechanisms, and modes of activity regulation. Furthermore, it explores the potential mechanisms by which DUB dysregulation contributes to endometrial and cervical carcinogenesis. Additionally, we present the successful application of DUB inhibitors in the treatment of malignancies and provide an analysis of the current research status regarding targeted therapies for EC and CC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149988"},"PeriodicalIF":2.4,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}