Genes & Diseases最新文献

{"title":"Salt-inducible kinase 1 is a key gene in suppressing EVD68-induced asthma by modulating antiviral immunity","authors":"Juntong Liu ,&nbsp;Yue Wang ,&nbsp;Lingyun Zou ,&nbsp;Xinyue Han ,&nbsp;Mingqi Lv ,&nbsp;Xichuan Deng ,&nbsp;Jingjing Liao ,&nbsp;Guangchao Zang ,&nbsp;Lei Xu ,&nbsp;Tianle Gu ,&nbsp;Nan Lu ,&nbsp;Guangyuan Zhang","doi":"10.1016/j.gendis.2025.101845","DOIUrl":"10.1016/j.gendis.2025.101845","url":null,"abstract":"<div><div>Asthma is a complex inflammatory disease of the airways, affecting over 300 million individuals globally. Infection with enterovirus D68 (EV-D68) has been identified as a risk factor for asthma. However, the biological mechanisms of EV-D68-related asthma remain unclear. In this study, using machine learning techniques, we identified salt-inducible kinase 1 (SIK1), which plays a crucial role in associating with the asthma phenotype and EV-D68 infection. Concretely, a negative correlation between SIK1 expression and asthma risk has been revealed through Mendelian randomization. Immune infiltration analyses showed that SIK1 was negatively correlated with mast cell activity and positively correlated with T cell responses. Using weighted gene co-expression network analysis, we demonstrated SIK1's role in antiviral immune responses in asthma. Further <em>in vitro</em> and <em>in vivo</em> experiments confirmed that SIK1 was up-regulated in virus infection, and it exerted antiviral effects in various viral infections. Finally, in the asthma exacerbation model of HDM combined with EV-D68 infection, SIK1 activation effectively mitigated EV-D68-induced asthma exacerbation in mice. Taken together, our findings suggest that SIK1 serves as a protective factor in EV-D68-induced asthma by modulating antiviral immune responses, which provide new insights into potential treatments for EV-D68-induced asthma attacks.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101845"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic druggable genome-wide analysis to identify potential therapeutic targets for urologic diseases","authors":"Yongwang Shi ,&nbsp;Hongyan Chen ,&nbsp;Xinlei Zhang,&nbsp;Chengliang Yin,&nbsp;Penghu Lian","doi":"10.1016/j.gendis.2025.101922","DOIUrl":"10.1016/j.gendis.2025.101922","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101922"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced transcriptomic profiling of esophageal tissue through optimized PAXgene fixation protocols","authors":"Fadi Charara ,&nbsp;Louison Descampe ,&nbsp;Ligia Craciun ,&nbsp;Laurine Verset ,&nbsp;Alexandre Spinette ,&nbsp;Meriem Ennaji ,&nbsp;Maarten Vander Kuylen ,&nbsp;Calliope Maris ,&nbsp;Pieter Demetter ,&nbsp;Benjamin Beck","doi":"10.1016/j.gendis.2025.101842","DOIUrl":"10.1016/j.gendis.2025.101842","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101842"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomic characterization of the pathologic niche in a patient with pulmonary crystal-storing histiocytosis","authors":"Yao Chen ,&nbsp;Zhining Huang ,&nbsp;Gaoxiang Wang ,&nbsp;Mingsheng Wu ,&nbsp;Xiao Chen ,&nbsp;Xiaohui Sun ,&nbsp;Lei Gao ,&nbsp;Mingran Xie","doi":"10.1016/j.gendis.2025.101904","DOIUrl":"10.1016/j.gendis.2025.101904","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101904"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer’s disease","authors":"Tingting Liu ,&nbsp;Zongting Rong ,&nbsp;Jingwen Li,&nbsp;Haojie Wu,&nbsp;Jianshe Wei","doi":"10.1016/j.gendis.2025.101846","DOIUrl":"10.1016/j.gendis.2025.101846","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss, with its pathogenesis tightly linked to a “pathological triad”—mitochondrial dysfunction, metabolic dysregulation, and calcium homeostasis imbalance. This triad forms a mutually reinforcing network that amplifies AD pathology, yet its precise causal relationships and clinical relevance remain incompletely understood. Here, we critically synthesize evidence from human studies, animal models, and <em>in vitro</em> systems to dissect how these dysfunctions interact <em>in vivo</em>: mitochondrial structural damage and bioenergetic failure (e.g., reduced cytochrome c oxidase activity) impair ATP production, triggering metabolic reprogramming (e.g., astrocytic Warburg-like glycolysis, lactate shuttle dysfunction) and disrupting calcium buffering via mitochondrial calcium uniporter (MCU) dysregulation. Conversely, metabolic stress (e.g., hyperglycemia-induced mitochondrial overload) and calcium overload (e.g., NMDA receptor hyperactivation) exacerbate mitochondrial damage through reactive oxygen species (ROS) bursts and mitochondrial permeability transition pore (mPTP) opening. These processes are further amplified by amyloid β-protein (Aβ) and tau pathology: Aβ oligomers directly inhibit mitochondrial respiration and activate calcium channels, while hyperphosphorylated tau disrupts mitochondrial trafficking and exacerbates metabolic enzyme dysfunction. We evaluate the clinical translatability of preclinical findings, highlighting inconsistencies (e.g., conflicting results of CoQ10 trials) and gaps (e.g., human-specific metabolic signatures). Finally, we propose a framework prioritizing multi-target therapies that disrupt the triad’s vicious cycle, emphasizing the need for biomarkers to stratify patients based on triad dysregulation patterns.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101846"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo multiplexed modeling reveals diverse roles of the TBX2 subfamily and Egr1 in Kras-driven lung adenocarcinoma","authors":"Athar Khalil ,&nbsp;Trang Dinh ,&nbsp;Meaghan Parks ,&nbsp;Rebecca C. Obeng ,&nbsp;Berkley Gryder ,&nbsp;Adam Kresak ,&nbsp;Yuxiang Wang ,&nbsp;Jeff Maltas ,&nbsp;Madeline Bedrock ,&nbsp;Xiangzhen Wei ,&nbsp;Zachary Faber ,&nbsp;Mira Rahm ,&nbsp;Jacob Scott ,&nbsp;Thomas LaFramboise ,&nbsp;Zhenghe Wang ,&nbsp;Christopher McFarland","doi":"10.1016/j.gendis.2025.101840","DOIUrl":"10.1016/j.gendis.2025.101840","url":null,"abstract":"<div><div>The TBX2 subfamily of T-box transcription factors (<em>e.g.</em>, <em>Tbx2</em>, <em>Tbx3</em>, <em>Tbx4</em>, <em>Tbx5</em>) plays an essential role in lung development. Down-regulation of these genes in human lung adenocarcinoma suggests that these genes may be tumor-suppressive; however, because down-regulation appears to occur primarily via epigenetic change, it remains unclear if these changes causally drive tumor progression or are merely the consequence of upstream events. Herein, we developed the first multiplexed mouse model to study the impact of TBX2 subfamily loss, alongside associated signaling genes (<em>Egr1</em>, <em>Chd2</em>, <em>Tnfaip3a</em>, and <em>Atf3</em>) in <em>Ras</em>-driven lung cancer. Using tumor-barcoding with high-throughput barcode sequencing (TuBa-seq), a high-throughput tumor-barcoding system, we quantified the growth effects of these knockouts during early and late tumorigenesis. <em>Chd2</em> knockout suppressed both tumor initiation and progression, whereas <em>Tnfaip3</em> knockout enhanced tumor initiation and overall tumor growth. <em>Tbx2</em> loss showed stage-specific effects on tumor development. Notably, <em>Egr1</em> emerged as a strong tumor suppressor and its knockout resulted in approximately a fivefold increase in tumor size at 20 weeks (two-sample <em>t</em>-test, <em>p</em> &lt; 0.05), exceeding the impact observed with <em>Rb1</em> loss. Transcriptomic analyses of <em>Egr1</em>-deficient tumors suggested immune dysregulation, including heightened inflammation and potential markers of T cell exhaustion in the tumor microenvironment. These findings indicate that <em>Egr1</em> may play a role in suppressing tumor growth through modulating immune dynamics, offering new insights into the interplay between tumor progression and immune regulation in lung adenocarcinoma.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101840"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRG4 suppresses breast cancer metastasis via ERBB4-YAP1-mediated down-regulation of MMPs","authors":"Saijun Wang ,&nbsp;Mingwei Guo ,&nbsp;Lingyun Xu ,&nbsp;Jiaming Xue ,&nbsp;Shuai Chen ,&nbsp;Ke Xu ,&nbsp;Yan Zhou ,&nbsp;Aihua Gu ,&nbsp;Wei Gao ,&nbsp;Jianwei Zhou ,&nbsp;Yi Zhang ,&nbsp;Liming Tang ,&nbsp;Dongmei Wang","doi":"10.1016/j.gendis.2025.101691","DOIUrl":"10.1016/j.gendis.2025.101691","url":null,"abstract":"<div><div>Obesity exacerbates breast cancer metastasis, yet the underlying mechanisms remain incompletely understood. Here, we identify neuregulin 4 (NRG4), a ligand of Erb-B2 receptor tyrosine kinase 4 (ERBB4), as a key regulator of metastasis, through the ERBB4-YAP1 signaling axis. Using MMTV-PyMT and 4T1 breast cancer models, we demonstrate that obesity accelerates metastasis, while NRG4, secreted by inguinal white adipose tissue (iWAT), inhibits cancer cell migration and epithelial–mesenchymal transition (EMT). Mechanistically, NRG4 activates ERBB4, producing a cleaved pERBB4 fragment that interacts with phosphorylated YAP1 (pYAP1), restricting its nuclear translocation. RNA sequencing revealed that NRG4 suppressed the transcription of Mmp9 and Mmp12, which encode matrix metalloproteinases critical for extracellular matrix remodeling and invasion. Co- immunoprecipitation and promoter assay confirmed that YAP1 bound to TEAD1 and activated MMP9/MMP12 transcription in the absence of NRG4. Importantly, recombinant NRG4 (rNRG4) reduced the growth and invasiveness of breast cancer organoids. These findings establish NRG4 as a metastasis suppressor in obesity-associated breast cancer by inhibiting the ERBB4-YAP1 pathway and down-regulating matrix metalloproteinases. Our study highlights the therapeutic potential of targeting NRG4-ERBB4 signaling to mitigate obesity-driven breast cancer progression.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101691"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications","authors":"Yongle Xu ,&nbsp;Shuangyue Ma ,&nbsp;Manyi Xu ,&nbsp;Hongbo Zhu ,&nbsp;Yuncong Wang ,&nbsp;Wenbo Dong ,&nbsp;Jing Gan ,&nbsp;Yusen Zhao ,&nbsp;Xinrong Li ,&nbsp;Shuangshuang Wang ,&nbsp;Haoyu Hu ,&nbsp;Jiaheng He ,&nbsp;Shangwei Ning ,&nbsp;Hui Zhi","doi":"10.1016/j.gendis.2025.101832","DOIUrl":"10.1016/j.gendis.2025.101832","url":null,"abstract":"<div><div>5-Methylcytosine (5-mC) is the most prevalent DNA methylation modification in the human genome, and its abnormal patterns are strongly associated with tumor progression. Intratumoral and intertumoral DNA methylation heterogeneity (DNAmeH) primarily arises from cancer epigenome heterogeneity and the diverse cell compositions within the tumor microenvironment (TME). Furthermore, recent advancements in high-throughput sequencing and microarray technologies have facilitated the development of quantitative methods for measuring DNAmeH, enabling a more thorough exploration of the factors influencing it. Moreover, investigating various DNA methylation patterns at the single-cell level within the intricate TME sheds light on DNAmeH being driven by cellular heterogeneity. In addition, accumulating studies on the selection of methylation biomarkers in tissue or circulating DNA elucidate the cell specificity of DNA methylation, which is valuable for early cancer detection and personalized therapy. In this review, we elucidate the characteristics of intratumoral and intertumoral DNAmeH, considering DNAmeH differences across cancer types, among individual cells, and at allele-specific hemimethylation sites. Several metrics are summarized to quantitatively assess DNAmeH. We evaluate the factors that influence DNAmeH via these metrics, including the cell cycle phase, tumor mutational burden (TMB), cellular stemness, copy number variation (CNV), tumor subtype, tumor characteristics, tumor stage, state of tumor cells, hypoxia, and tumor purity. Finally, we highlight the deconvolution of TME cellular components and the application of predictive methylation biomarkers in cancer clinical research.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101832"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TTI1 indicates a poor prognosis and is associated with metastasis and immunosuppression of colorectal cancer","authors":"Xiangwen Tan ,&nbsp;Yunhua Xu ,&nbsp;Shuxiang Li ,&nbsp;Qing Fang ,&nbsp;Guang Fu ,&nbsp;Qiulin Huang ,&nbsp;Desi Shang ,&nbsp;Kai Fu ,&nbsp;Yufei Lv ,&nbsp;Shuai Xiao","doi":"10.1016/j.gendis.2025.101727","DOIUrl":"10.1016/j.gendis.2025.101727","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101727"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBM15 in diseases: Molecular mechanisms and clinical opportunities from RNA m6A methylation","authors":"Fengze Li ,&nbsp;Junzhe Liu ,&nbsp;Na Wang ,&nbsp;Zhihong Zhou ,&nbsp;Linzhen Huang ,&nbsp;Qiankun Ji ,&nbsp;Jingying Li","doi":"10.1016/j.gendis.2025.101901","DOIUrl":"10.1016/j.gendis.2025.101901","url":null,"abstract":"<div><div>RNA m⁶A methylation is the most common type of RNA modification, and RBM15 regulates various cellular processes by writing m⁶A methylation on RNA. m⁶A methylation mediated by RBM15 significantly affects RNA stability and translational efficiency, thereby regulating gene expression. In-depth studies have revealed that RBM15 affects the progression of various diseases by regulating the expression of multiple genes, and its m⁶A methylation modification process is also considered to be an effective therapeutic target. In this paper, we review the latest research progress on the regulation of m⁶A methylation modification of RBM15, its molecular regulation in various diseases, such as cancer and metabolic diseases, and the potential therapeutic drugs derived from it, with a view to providing therapeutic strategies for the subsequent research on RBM15 and gene therapy targeting RBM15.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101901"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}