Gene最新文献

{"title":"Under the dual hit: genetic and phenotypic analysis of a Han family with severe adolescent cirrhosis from the convergence of Wilson’s disease and favism","authors":"Yu-qin Xie ,&nbsp;Zi-yan Xu ,&nbsp;Hong Lin ,&nbsp;Li-jun Xie ,&nbsp;Jie-wei Luo ,&nbsp;Li-jun Zhang ,&nbsp;Zhi-hai Zheng","doi":"10.1016/j.gene.2025.149953","DOIUrl":"10.1016/j.gene.2025.149953","url":null,"abstract":"<div><div>Hepatolenticular degeneration (HLD, MIM:277900) is an autosomal recessive disorder characterized by excessive copper accumulation in hepatocytes, leading to hepatic and neurological abnormalities, hepatocellular injury, neurodegeneration, and copper deposition in the cornea. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic cause of hemolytic anemia, which can be triggered by chronic conditions, drugs, food, or infections, and exhibits highly variable severity. In some cases, multiple genetic factors may collectively influence disease presentation and progression. This study reports a proband who developed abnormal liver function at age 20. Four years later, she exhibited severe jaundice, liver dysfunction, serous effusions, anemia, and Kayser–Fleischer rings, leading to diagnoses including decompensated cirrhosis, splenomegaly, suspected HLD, hemolytic anemia, portal hypertension, hypoproteinemia, low T3 syndrome, primary peritonitis, and gallstones with cholecystitis. Genetic screening identified two pathogenic heterozygous variants in ATP7B (NM_000053.4): c.2128G &gt; A (p.G710S) in exon 8 and c.525dupA (p.V176Sfs*28) in exon 2, together forming a compound heterozygous mutation. Additionally, a heterozygous mutation in G6PD (NM_001360016.2), c.1388G &gt; A (p.R463H) in exon 12, was found. Family members carrying the G6PD variant showed recurrent benign jaundice or remained asymptomatic. A heterozygous missense variant of uncertain significance, c.205C &gt; T (p.R69C), was also detected in exon 3 of STEAP3 (NM_182915.3), a gene linked to hypochromic microcytic anemia with iron overload type 2 (MIM#615234). This rare variant was predicted to be deleterious by in silico tools, suggesting possible genetic cosegregation.</div><div>SWISS-MODEL analysis indicated that these variants may alter the three-dimensional structures of the copper-transporting ATPase and G6PD proteins, potentially impairing function—particularly the frameshift mutation p.V176Sfs*28. We hypothesize that the accumulation of multiple pathogenic genetic factors resulted in a “double-hit” effect, leading to the patient’s severe phenotypes, including advanced liver cirrhosis and hemolytic anemia. Elucidating such multi-gene “double-hit” mechanisms may enhance the understanding of gene–gene interactions in complex diseases.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149953"},"PeriodicalIF":2.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780827","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":"Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function","authors":"Mian Feng ,&nbsp;Thomas J. Hall ,&nbsp;David E. MacHugh ,&nbsp;Lisa M. Katz ,&nbsp;Emmeline W. Hill","doi":"10.1016/j.gene.2025.149951","DOIUrl":"10.1016/j.gene.2025.149951","url":null,"abstract":"<div><div>Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrichment analysis revealed that the DEGs were primarily associated with terms related to muscle assembly and system development, including <em>Developmental process (GO:0032502</em>)<em>, Anatomical structure development (GO:0048856</em>)<em>, Actin cytoskeleton (GO:0015629</em>)<em>, and Growth factor binding (GO:0019838</em>)<em>.</em> KEGG pathway analysis indicated that <em>ECM-receptor interaction</em>, <em>Protein digestion and absorption</em>, <em>Focal adhesion</em>, and <em>PI3K-Akt signalling pathway</em> were the significant functional pathways. Protein-protein interaction network and hub gene analyses identified seven key regulatory genes: <em>COL1A1, COL1A2, COL3A1, S100A4, NOTCH1, THY1</em> and <em>MT-ND2.</em> In addition, the <em>MSTN, COL4A1, COL4A2, SPEN, S100A4, NOTCH1, NOTCH3, and THY1</em> genes were found to play key roles in the functional development of skeletal muscle. This study provides insight into the transcriptional landscape of skeletal muscle development in young Thoroughbred horses. The period between two and three years of age represents a crucial stage in skeletal muscle adaptation in the juvenile horse, with a particular emphasis on muscle structural and functional integrity.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149951"},"PeriodicalIF":2.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774290","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 and epigenetic determinants of injury risk and recovery in elite athletes: toward precision sports medicine","authors":"Hao Ding ,&nbsp;Qilu Deng ,&nbsp;Zhenhua Guo","doi":"10.1016/j.gene.2025.149957","DOIUrl":"10.1016/j.gene.2025.149957","url":null,"abstract":"<div><div>Musculoskeletal injuries and interindividual variability in recovery remain critical challenges for sustaining elite athletic performance. Despite advances in diagnostics, training, and rehabilitation, unexplained differences in injury risk and recovery efficiency persist. Growing evidence implicates genetic and epigenetic mechanisms in these disparities, influencing collagen integrity, inflammatory regulation, oxidative stress, and muscle regeneration. Key contributors include single-nucleotide polymorphisms (SNPs) in COL1A1, COL5A1, ACTN3, and IL6, as well as novel loci identified by genome-wide association studies (GWAS). Polygenic risk scores (PRS), which integrate the effects of multiple low-impact variants, enhance prediction compared to single-gene markers. Epigenetic regulators, including DNA methylation and exercise-responsive microRNAs (e.g., miR-206, miR-133a, miR-486), provide a dynamic interface linking genetic predisposition with environmental factors such as training load and nutrition. Integration of genomic data with wearable technologies and artificial intelligence enables real-time monitoring, adaptive recovery, and precision load management. Yet, clinical translation faces challenges including limited population diversity, interpretative complexity, and ethical concerns over data privacy and potential misuse. Advancing precision sports medicine will require multidisciplinary, systems-level strategies that unite molecular insights with practical implementation, ultimately enabling individualized injury prevention, optimized rehabilitation, and the preservation of long-term athlete health and performance.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149957"},"PeriodicalIF":2.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755941","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":"2025-12-12","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":"Two transcription factors and one antisense RNA underlie the thermoregulated insect pathogenicity of Yersinia entomophaga MH96","authors":"Amber R. Paulson ,&nbsp;Maureen O’Callaghan ,&nbsp;Xue-Xian Zhang ,&nbsp;Naran Naren ,&nbsp;Marion Schoof ,&nbsp;Mark R.H. Hurst","doi":"10.1016/j.gene.2025.149955","DOIUrl":"10.1016/j.gene.2025.149955","url":null,"abstract":"<div><div>Entomopathogenic bacteria express virulence genes in a temperature-dependent manner, but the underlying molecular mechanisms remain poorly understood. Here, we describe the roles of an unusual LytTR-containing transcription factor Yen6 in determining the virulence of <em>Yersinia entomophaga</em> (MH96). An initial transcriptome analysis <em>in vivo</em> revealed that <em>yen6</em>, located 1,372 bp upstream from genes encoding the Yen Toxin complex (Yen-Tc), exhibited significantly higher transcriptional activity at 37 °C compared to 25 °C (adjusted <em>p</em>-value &lt; 0.001) during intrahemocoelic infection in the insect model <em>Galleria‍ mellonella</em>. Deletion of <em>yen6</em> also significantly reduced MH96′s virulence in <em>G.‍‍ mellonella</em> by up to three-fold. Next, comparing the transcriptome of wild-type MH96 and its derived Δ<em>yen6</em> mutant revealed genes for ribose utilization were downregulated whereas genes for fructose utilization and the RNA-binding protein YhbY were upregulated in the <em>yen6-</em>deficient mutant. Subsequent electromobility shift assays showed that purified Yen6_His6 protein was capable of specifically binding to the promoter regions of the ribose and fructose utilization-related gene clusters, as well as <em>yhbY</em>. A 645-nucleotide-long 3′ untranslated region, designated <em>yen7_AS</em>, was identified extending from the <em>yen6</em> coding region. Notably, <em>yen7_AS</em> completely overlaps the <em>yen7</em> gene on the opposing strand and may therefore act as a <em>cis</em> anti-sense RNA regulating <em>yen7</em> expression, which encodes a putative transcriptional regulator of the Yen-Tc. This study highlights the critical role of the <em>yen6–yen7</em> locus in MH96 virulence during <em>G.‍ mellonella</em> infection<em>,</em> including the complex mechanisms controlling insecticidal exoprotein production.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149955"},"PeriodicalIF":2.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752086","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":"Genome-wide association study of tolerance to acute hypoxia in the olive flounder (Paralichthys olivaceus) using individual blood cortisol levels as a physiological phenotype","authors":"M.A.H. Dilshan ,&nbsp;Gaeun Kim ,&nbsp;W.K.M. Omeka ,&nbsp;D.S. Liyanage ,&nbsp;H.M.V. Udayantha ,&nbsp;D.C.G. Rodrigo ,&nbsp;G.A.N.P. Ganepola ,&nbsp;H.A.C.R. Hanchapola ,&nbsp;Y.K. Kodagoda ,&nbsp;Po Gong ,&nbsp;Jihun Lee ,&nbsp;Sukkyoung Lee ,&nbsp;Jeongeun Kim ,&nbsp;Jehee Lee","doi":"10.1016/j.gene.2025.149952","DOIUrl":"10.1016/j.gene.2025.149952","url":null,"abstract":"<div><div>Hypoxia, caused by reduced dissolved oxygen (DO) levels in water, is a critical challenge in aquaculture and often results in stress, anorexia, and mass mortality in fish. The olive flounder (<em>Paralichthys olivaceus</em>) is a key species in South Korea’s global aquaculture exports. However, aquaculture production of <em>P. olivaceus</em> experiences significant economic losses caused by hypoxia-induced fish mortality, highlighting the critical need for developing genetically improved hypoxia-tolerant strains. In this study, a genome-wide association study (GWAS) was performed to unveil single-nucleotide polymorphisms (SNPs) associated with acute hypoxia tolerance and elucidate underlying regulatory mechanisms. A total of 382 <em>P. olivaceus</em> fish were measured for blood serum cortisol level using enzyme-linked immunosorbent assay (ELISA) upon acute hypoxia stress. Blood plasma cortisol levels were used as a proxy phenotype of hypoxia tolerance, with the hypothesis that elevated concentrations indicate low tolerance, and minimized concentrations indicate high tolerance to acute hypoxia stress. Then, fish were genotyped using the Affymetrix® Axiom® myDesign™ genotype array, and 57,651 SNPs were retained after quality control filtering. A significant SNP was identified on chromosome 15 of the <em>P. olivaceus</em> genome, above the suggestive threshold (<em>p</em> &lt; 1 × 10⁻⁴) for the stress cortisol level trait. A strongly associated SNP with accession number AX-419149718 was located in the zona pellucida-like domain-containing protein 1 (<em>Zpld1</em>) gene. Gene ontology (GO) analysis suggests that <em>Zpld1</em> is involved in signaling pathways, including the integrin-mediated signaling pathway, thereby contributing to the mitigation of hypoxia stress effects. Collectively, this study provides insights into the genetic basis of acute hypoxia tolerance in <em>P. olivaceus</em> and may serve as a foundation for establishing genomic selection of olive flounders with acute hypoxia stress tolerance in aquaculture breeding programs.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149952"},"PeriodicalIF":2.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735922","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":"Differential genomic signatures of homozygosity and a haplotype sharing Extents across breeds associated with body size variation in Korean indigenous goats","authors":"Seongmin Kim ,&nbsp;Hankyeol Jeong ,&nbsp;Ga-Eun Kim ,&nbsp;Kwan-Woo Kim ,&nbsp;Woncheoul Park ,&nbsp;Jaemin Kim ,&nbsp;Bong-Hwan Choi","doi":"10.1016/j.gene.2025.149956","DOIUrl":"10.1016/j.gene.2025.149956","url":null,"abstract":"<div><div>Korean indigenous goats are maintained as purebred lineages in geographically isolated populations such as Dangjin, Gyeongsang National University (GNU), Jangsu, and Tongyeong. However, their small population size and high rates of inbreeding have raised concerns regarding the preservation of genetic diversity. We generated SNP genotypes for 217 Korean indigenous goats using the GoatSNP50 BeadChip, and standardized body size measurements with complete metadata were available for 64 adult individuals. Principal component analysis (PCA) clearly separated the four lineages, with the GNU population showing particularly high values of inbreeding coefficient and proportion of runs of homozygosity, reflecting the impact of recent closed breeding. Genome-wide patterns of haplotype sharing revealed exploratory trends suggesting that introgression from global breeds tended to coincide with larger body size, whereas intensified inbreeding within the Korean population showed a general tendency toward reduced body size. Furthermore, cross-population extended haplotype homozygosity (XP-EHH) analysis revealed candidate genes, including <em>ADGRL3</em>, <em>SP8</em>, and <em>ARL6IP5</em> that are likely involved in adaptation to seasonal environmental stress. Our findings highlight the global connectivity, functional relevance of body conformation traits, and selective signatures of Korean indigenous goats, providing a genomic foundation for preserving diversity and guiding future breeding.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149956"},"PeriodicalIF":2.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752089","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":"Inorganic nitrogen sources and light cooperatively stimulate gene regulation for non-photosynthetic phosphoenolpyruvate carboxylase in wheat leaves","authors":"Naoki Yamamoto ,&nbsp;Jingru Jiang ,&nbsp;Haoyu Deng ,&nbsp;Ken-ichi Kurotani ,&nbsp;Jiang Zou ,&nbsp;Zaijun Yang","doi":"10.1016/j.gene.2025.149950","DOIUrl":"10.1016/j.gene.2025.149950","url":null,"abstract":"<div><div>Phospho<em>enol</em>pyruvate carboxylase (PEPC) is a bicarbonate fixation enzyme that is associated with nitrogen metabolism. We previously observed that NO₃^– affected the expression levels of <em>PEPC</em> genes differently in detached wheat leaves. Three types of <em>PEPC</em> isogenes, including the orthologous isogene group (<em>Tappc1b</em>) for C₄-photosynthetic <em>PEPC</em>, exhibited distinct transcriptionally up-regulated patterns from one another. However, it remains unclear which nitrogen compounds exactly trigger the gene expression responses and their light dependency. Here, we investigated the cause of isogene-specific expression responses of <em>PEPCs</em> to different forms of nitrogen supplementation. Detached leaves from wheat seedlings cultivated under a nitrogen-deficient condition were incubated with NO₃^–, NH₄⁺, and urea under both light and dark conditions. Notably, the genes analyzed exhibited markedly different expression patterns across the nitrogen forms under the light condition. <em>Tappc1a</em>, which did non-respond to NO₃^–, was up-regulated by NH₄⁺ exclusively under light. <em>Tappc2</em> was also up-regulated by NO₃^– and NH₄⁺ only under light, and these up-regulations were suppressed under the dark condition. The candidate transcriptional regulator <em>DOF1</em> for <em>Tappc1b</em> in wheat was also up-regulated by NO₃^– only under light condition, but earlier than <em>Tappc1b</em>, implicating a DOF1-mediated transcriptional response of <em>Tappc1b</em> to NO₃^–. Comparison of <em>Tappc1b</em> promoter sequences with that of NO₃^–-responsive maize C₄ <em>PEPC</em> revealed conserved light-responsive elements near the Dof1 binding site. These findings suggest that distinct transcriptional regulatory cascades would exist for non-photosynthetic <em>PEPCs</em> in response to different inorganic nitrogen forms.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149950"},"PeriodicalIF":2.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741963","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":"Gene therapy for Krabbe disease: evidence from mouse and canine models","authors":"Yang Li ,&nbsp;Xiang Dong ,&nbsp;Jian Guo ,&nbsp;Ya-feng Lv","doi":"10.1016/j.gene.2025.149949","DOIUrl":"10.1016/j.gene.2025.149949","url":null,"abstract":"<div><div>Globoid cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-galactosylceramidase<!--> <!-->(<em>GALC</em>) gene, resulting in enzyme deficiency and the progressive accumulation of galactosylsphingosine and galactosylceramide in the white matter of the central nervous system and in peripheral nerves, which in turn triggers demyelination. Although no curative therapy is currently available, studies in animal models in recent years have shown that gene therapy can ameliorate pathological and biochemical abnormalities and holds considerable promise for clinical translation. This article reviews advances in gene therapy in animal models of GLD and discusses key directions and challenges for future treatments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149949"},"PeriodicalIF":2.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741704","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":"Comprehensive transcriptomic profiling reveals lncRNA–miRNA–mRNA regulatory networks in skeletal muscle aging of mice","authors":"Jinrui Jia,&nbsp;Qingyan Wang,&nbsp;Xuanye Jiang,&nbsp;Hao Chen,&nbsp;Minwei Huang,&nbsp;Bing Ni,&nbsp;Huiying Zhang,&nbsp;Xin’e Shi,&nbsp;Jianjun Jin","doi":"10.1016/j.gene.2025.149946","DOIUrl":"10.1016/j.gene.2025.149946","url":null,"abstract":"<div><h3>Purpose</h3><div>As organisms age, physiological and pathological changes occur, with altered lncRNA expression playing a key role. However, their regulatory mechanisms in aging remain unclear. This study investigates the differential expression of lncRNAs between aged and young mice, and explores the lncRNA–miRNA–mRNA interplay to gain insights into the molecular basis of aging.</div></div><div><h3>Methods</h3><div>We performed whole-transcriptome sequencing on tibialis anterior muscles from four aged (20-month-old) and four young (3-month-old) mice. Hub genes were identified via PPI and WGCNA analyses, followed by functional enrichment. Integrative analysis revealed interactions among differentially expressed lncRNAs, miRNAs, and mRNAs, leading to the construction of cis-/<em>trans</em>-regulatory and ceRNA networks.</div></div><div><h3>Results</h3><div>Our results revealed 746 significantly differentially expressed known lncRNAs (465 upregulated, 281 downregulated) and 27 novel lncRNAs in aged mouse TA muscle, alongside 50 miRNAs and 1124 mRNAs. Based on lncRNA classification (antisense, intergenic, intronic), we constructed subtype-specific cis- and <em>trans</em>-regulatory networks. Hub genes were identified via PPI and WGCNA analyses to further refine these networks. Highly expressed and variable genes were also integrated into regulatory mapping. Enrichment analyses indicated involvement in extracellular matrix remodeling, epithelial cell migration, and immune response.</div></div><div><h3>Conclusions</h3><div>This study systematically profiled age-related changes in lncRNAs, miRNAs, and mRNAs in TA muscle, and constructed core regulatory networks based on lncRNA subtypes. This study systematically profiled age-related transcriptomic changes in mouse skeletal muscle and constructed lncRNA–miRNA–mRNA regulatory networks associated with aging. These results provide a valuable resource and generate hypotheses for future experimental validation of lncRNA-mediated regulatory mechanisms in muscle aging.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149946"},"PeriodicalIF":2.4,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145722080","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}