Gene最新文献

{"title":"TRPV4-mediated mechanotransduction of matrix stiffness in the pathogenesis, progression, and malignant transformation of oral submucous fibrosis","authors":"Sampurna Raha,&nbsp;Rajiv S. Desai,&nbsp;Shivani P. Bansal,&nbsp;Pankaj M. Shirsat,&nbsp;Pooja S. Prasad","doi":"10.1016/j.gene.2025.149936","DOIUrl":"10.1016/j.gene.2025.149936","url":null,"abstract":"<div><div>Oral Submucous Fibrosis (OSF) is a long-standing, scarring, inflammatory, potentially malignant disorder induced by areca nut. The transient receptor potential vanilloid 4 (TRPV4), a cation channel permeable to Ca²⁺, in the TRPV family, is implicated in wound healing, fibrotic changes and malignancy, but its role as a mechanosensor for matrix-stiffness and stress in OSF and its malignant transformation to oral squamous cell carcinoma (OSCC) remains unexplored. The current research sought to investigate the probable involvement of TRPV4 in the onset different OSF stages and its progression to malignancy by immunohistochemistry. Primary antibodies targeting TRPV4 were applied to formalin-fixed paraffin-embedded blocks from ten cases for each category: (a) Stage-1 OSF, (b) Stage 2 OSF, (c) Stage 3 OSF, (d) Stage 4 OSF, (e) OSCC + OSF, and (vi) OSCC − OSF. Additionally, buccal mucosa tissues from ten healthy individuals (NOM) were utilized as control. Mean epithelial quick scores of TRPV4 in NOM, Stages 1–4 OSF, and OSCC with and without OSF were 1.2, 2.5, 3.9, 4.5, 4.6, 5.8, and 6.2, while connective tissue scores were 1.5, 3.5, 4.1, 4.7, 5.3, 5.9, and 6.5, respectively. TRPV4 expression was upregulated in Stages 3 OSF and 4 OSF and OSCC in the presence or absence of OSF compared to NOM and Stage 1 and 2 OSF. This study evaluates the unpaved role of TRPV4 in OSF, mediated by various canonical pathways, contributing to its development by increasing matrix-stiffness and rigidity, which further upregulates TRPV4 expression, ultimately facilitating carcinogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149936"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696051","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":"Editors’ Corner: Suppressor of cytokine signaling 6 (SOCS6) mediates ubiquitination-dependent degradation of SLC7A11 to promote ferroptosis in ovarian cancer","authors":"Xavier Graña","doi":"10.1016/j.gene.2025.149937","DOIUrl":"10.1016/j.gene.2025.149937","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149937"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707324","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":"Reassessing the tmRNA-SmpB complex as a virulence determinant","authors":"T. Nagarajan ,&nbsp;N. Arulmuthu Kumaran","doi":"10.1016/j.gene.2025.149928","DOIUrl":"10.1016/j.gene.2025.149928","url":null,"abstract":"<div><div>Rescuing stalled ribosomes from the truncated mRNA is identified as a crucial process for the survival of a bacterial cell. A small RNA named tmRNA (transfer messenger RNA), and protein SmpB (Small protein B), together constitute a ribosome rescue apparatus which is ubiquitous among most of the eubacteria. tmRNA mediated ribosome rescue process (also called <em>trans</em>-translation) has been found to be the major pathway of clearance of stalled ribosome complexes. In the process, tmRNA-SmpB complex recycles stalled ribosomes by making them undergo normal translation and termination. Apart from rescuing stalled ribosomes, <em>trans</em>-translation modulates other cellular pathways (such as cell cycle, oxidative stress, nutritional stress, DNA damage response and so on) by regulating the intracellular level of various proteins. It becomes more and more obvious that the function of <em>trans</em>-translation apparatus is diverse and plays a role in bacterial pathogenesis also. This review will focus on the key findings on the involvement of tmRNA and its partner SmpB in regulation of pathogenesis and virulence in different pathogenic bacteria.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149928"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648023","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":"2026-02-10","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}

{"title":"Target of rapamycin (TOR) kinases in Leishmania: Insights from comparative analyses with Trypanosomatids","authors":"Soumi Chowdhury ,&nbsp;Harsh Pawar","doi":"10.1016/j.gene.2025.149933","DOIUrl":"10.1016/j.gene.2025.149933","url":null,"abstract":"<div><div>The Target of Rapamycin (TOR) kinase family is a central regulator of eukaryotic cell growth and metabolism. Unlike most eukaryotes that possess one or two TOR genes, <em>Leishmania</em> species encode four distinct paralogs, suggesting lineage-specific expansion and functional diversification. In this study, we performed a comprehensive phylogenetic and domain analysis of TOR paralogs across multiple <em>Leishmania</em> species, with <em>Trypanosoma brucei</em> serving as a comparative reference. TOR1 and TOR2 were found to be highly conserved, possessing canonical FAT, FRB, and PI3Kc domains, consistent with their roles in the essential TORC1 and TORC2 complexes. TOR3 and TOR4 displayed significant sequence divergence and altered domain structures, particularly in visceral and mucocutaneous species. TOR3 lacks the FRB domain but retains kinase activity and is implicated in arginine sensing and acidocalcisome biogenesis. TOR4 shows the highest divergence, including truncated domains and species-specific clustering, suggesting a role in parasite adaptation or stage differentiation. Functional annotations further support this, as TOR1 and TOR2 are enriched in kinase functions, while TOR3 and TOR4 are associated with hypothetical or uncharacterized proteins. The conserved PI3Kc domain across all paralogs offers a target for drug development. These findings enhance our understanding of TOR evolution and its therapeutic potential in leishmaniasis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149933"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713995","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":"CRISPR 2.0: Expanding the genome engineering Toolbox for epigenetics, RNA editing, and molecular diagnostics","authors":"Khushboo Pradhan ,&nbsp;Sindhu Anoop","doi":"10.1016/j.gene.2025.149938","DOIUrl":"10.1016/j.gene.2025.149938","url":null,"abstract":"<div><div>Non-canonical CRISPR systems adaptation has led to genome editing through nucleases, and the development of transcriptional and epigenetic regulation, transcriptome editing, and molecular diagnostics has resulted in a diversified set of tools—CRISPR 2.0. In this review, the author summarizes the mechanisms and recent engineering advances of (i) dCas9-based epigenetic effectors, (ii) RNA-targeting Cas13 systems and engineered RNA editors, (iii) DNA base editors and prime editors, and (iv) CRISPR-powered diagnostic platforms and their translational readiness. There is a critical comparison of the various approaches (e.g., RNAi/ASO versus Cas13-based methods; base editing versus prime editing) along with practical translational considerations such as delivery technologies, safety (off-target/edit windows, mosaicism), and regulatory pathways which are evaluated. Three concise case studies refer to map laboratory evidence to clinical or near-clinical outcomes and the ethical and governance discussion is widened to include global access, intellectual property and equity in deployment. Finally, the authors classify technologies according to their level of readiness — diagnostics and some ex-vivo therapeutic approaches are already in or very close to clinical use, chosen in-vivo editing methods are undergoing early trials, and AI-assisted nuclease design is still mostly theoretical but is getting better fast. This comprehensive viewpoint is intended to help researchers and physicians understand which CRISPR tools are most likely to be translated soon and where more validation is required.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149938"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696126","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":"Reference genes for quantitative real-time polymerase chain reaction in in vitro non-alcoholic fatty liver disease","authors":"Jingzhi Chen ,&nbsp;Xingmi Chen ,&nbsp;Ying Liu ,&nbsp;Chunming Lyu ,&nbsp;Ming Xu ,&nbsp;Yang Yang","doi":"10.1016/j.gene.2025.149931","DOIUrl":"10.1016/j.gene.2025.149931","url":null,"abstract":"<div><h3>Background</h3><div>In metabolic dysfunction-associated fatty liver disease (MAFLD) research, reference genes for qPCR are crucial but often unvalidated.</div></div><div><h3>Methods</h3><div>RNA-seq was performed in control and free fatty acid (FFA) treated AML12 cells, and the candidates for reference gene were selected by previous literatures and filtered by dual-index ranking via normalization of coefficient variation and Log₂FoldChange in the RNA-seq library. qPCR data was further analyzed via NormFinder, BestKeeper, geNorm, ΔCt and RefFinder to assess reference gene expression stability.</div></div><div><h3>Results</h3><div>FFA treated cells showed a significantly increased lipid droplet accumulation. RNA-seq dual-index ranking and RefFinder identified that <em>Ywhaz</em> was the most stable reference gene.</div></div><div><h3>Conclusion</h3><div>Our finding revealed that <em>Ywhaz</em> is the most stable reference gene for qPCR in the AML12 cell model of FFA-induced MAFLD, and provided a reliable procedure for screening reference genes.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149931"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667852","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 role of 3D preclinical models in the Era of precision medicine: A bladder cancer perspective","authors":"Carlotta Frascolla ,&nbsp;Riccardo Mastroianni ,&nbsp;Giuseppe Simone ,&nbsp;Giovanni Blandino","doi":"10.1016/j.gene.2025.149919","DOIUrl":"10.1016/j.gene.2025.149919","url":null,"abstract":"<div><div>Bladder cancer (BCa) remains one of the most challenging malignancies in oncology, driven by deep molecular heterogeneity, dynamic tumor evolution and complex tumor–microenvironment interactions. Despite advances in molecular characterization and the introduction of new treatments, translating biological knowledge into meaningful clinical benefits remains a major bottleneck. In recent years, next-generation 3D preclinical models have emerged as essential tools to recapitulate BCa complexity, offering new opportunities to investigate tumor biology and support the development of personalized treatment strategies. This review provides an overview of available 3D models for BCa, discusses their application and highlights their growing integration into clinical trials to guide real-time therapeutic decisions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149919"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616554","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 de novo INSR variant in Type A insulin resistance syndrome: familial investigation and genetic implications","authors":"Xin Lin ,&nbsp;Zi-yan Xu ,&nbsp;Li-jun Xie ,&nbsp;Juan Zhu ,&nbsp;Hong-ping Yu ,&nbsp;Ruo-li Wang ,&nbsp;Yi-jia Luo ,&nbsp;Jing Zou ,&nbsp;Jian-hui Zhang ,&nbsp;Qian Chen ,&nbsp;Peng-fei Wang ,&nbsp;Dan-dan Ruan ,&nbsp;Yan-feng Zhou ,&nbsp;Li Chen ,&nbsp;Fang-meng Huang ,&nbsp;Mei-zhu Gao ,&nbsp;Li Zhang ,&nbsp;Yun-fei Li ,&nbsp;Zhu-ting Fang ,&nbsp;Jue Wang ,&nbsp;Jie-wei Luo","doi":"10.1016/j.gene.2025.149934","DOIUrl":"10.1016/j.gene.2025.149934","url":null,"abstract":"<div><div>Type A insulin resistance syndrome (TAIRS) is a rare autosomal dominant disorder associated with variants in the Insulin Receptor (<em>INSR</em>) gene. It is characterized by insulin resistance, hyperandrogenism, and acanthosis nigricans. The severity of the condition may be influenced by homozygosity or heterozygosity, with some female patients being misdiagnosed with polycystic ovary syndrome (PCOS). A 13-year-old female proband from a family was identified with hyperinsulinemia, hyperandrogenism, acanthosis nigricans, hirsutism, acne, oligomenorrhea, and masculinization. Exome sequencing and Sanger sequencing confirmed that the proband was a carrier of the <em>INSR</em> (NM_000208.2): c.3734 T &gt; A(p.V1245E) variant. This variant is not listed in the Human Gene Mutation Database (HGMD) or ClinVar. The novel variant was predicted to be deleterious by the bioinformatic tools SIFT, MutationTaster, and Condel. According to the American College of Medical Genetics and Genomics (ACMG) criteria, it was evaluated as PM6, PM2_Supporting, and PP3, and classified as uncertain significance. The variant was not detected in the proband’s parents or other family members, all of whom lacked the associated clinical phenotypes. The p.V1245E variant was found to be a <em>de novo</em> variant. SWISS-MODEL analysis suggested that the p.V1245E variant induces structural changes in the three-dimensional configuration of the <em>INSR</em> protein, potentially impairing its normal function. RT-qPCR revealed a significant reduction in <em>INSR</em> mRNA expression in the proband. In a 293 T cell model transfected with lentivirus carrying the p.V1245E variant, both Western blotting and RT-qPCR demonstrated decreased <em>INSR</em> mRNA and protein expression, while immunofluorescence showed reduced <em>INSR</em> protein levels with altered localization. Therefore, the ACMG evaluation (PS2, PS3, PM2_Supporting, PP3) was further upgraded to pathogenic. In conclusion, this de novo variant represents the pathogenic variant responsible for TAIRS in this family, expanding the variant spectrum of the <em>INSR</em> gene.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149934"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707930","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":"Downregulation of Syncytin-2 expression in preeclamptic placentas is associated with DNA hypermethylation of the downstream CpG-rich region","authors":"Chun Feng ,&nbsp;Teng Zhang ,&nbsp;Yuan Li ,&nbsp;Yuyun Long ,&nbsp;Qian Meng ,&nbsp;Shi-Wen Jiang","doi":"10.1016/j.gene.2025.149932","DOIUrl":"10.1016/j.gene.2025.149932","url":null,"abstract":"<div><div>Syncytin-2 is an endogenous retroviral envelope protein constitutively expressed in human placental trophoblasts. As a membrane glycoprotein, Syncytin-2 together with Syncytin-1 mediates the fusion of mononucleated cytotrophoblasts to form multinucleated syncytiotrophoblasts. Syncytiotrophoblasts constitute the fetal-maternal interface important for fetal-maternal exchange, barrier and endocrine functions of the placenta. Besides the fusogenic function, Syncytin-2 also possesses an immunosuppressive activity. In this study, the results of quantitative PCR indicated that Syncytin-2 expression was downregulated in third-trimester preeclamptic placentas, which is consistent with the result of previous studies. Importantly, the results of Combined Bisulfite Restriction Assay (COBRA) suggested hypermethylation of the downstream CpG-rich region, but not the promoter/exon1/intron1 and exon2 CpG- rich regions of <em>SYN-2</em> gene in third-trimester preeclamptic placentas. Subsequent bisulfite conversion and PCR amplification, cloning and sequencing of the downstream CpG- rich region confirmed hypermethylation of the 4 CpGs in this region in preeclamptic placentas. Moreover, treatment of human choriocarcinoma BeWo cells with DNMT inhibitor ADC (5-aza-deoxycytidine) resulted in a dose-responsive demethylation of the downstream CpG-rich region and an increased <em>SYN-2</em> mRNA level. Thus, the hypermethylation of the downstream CpG-rich region closely correlated with the downregulation of Syncytin-2 expression in preeclamptic placentas. These new findings underscore the significance of epigenetic alterations in preeclamptic placentas, and facilitate a better understanding on the pathological mechanism of preeclampsia.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149932"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687167","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}