Pub Date : 2025-11-14DOI: 10.1016/j.gene.2025.149902
Juan Zhu , Zi-yan Xu , Hong-ping Yu , Ruo-li Wang , Yi-jia Luo , Li-jun Xie , Jian-hui Zhang , Qian Chen , Peng-fei Wang , Dan-dan Ruan , Jing Zou , Yan-feng Zhou , Li Chen , Fang-meng Huang , Mei-zhu Gao , Li Zhang , Yun-fei Li , Zhu-ting Fang , Li-sheng Liao , Xi-kui Zhang , Zhi-hai Zheng
This study identifies two pedigrees with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo PKD1 variants. Proband A carried a heterozygous splicing variant (c.9202-16G > A), presenting with bilateral renal cysts. The miniGENE assay confirmed this variant causes aberrant splicing with a 60-base excision, leading to a frameshift and a predicted truncated protein. Proband B carried a missense variant (c.2180 T > C; p.Leu727Pro), presenting with polycystic kidney and liver disease. Structural modeling revealed this variant severely disrupts local secondary structure and a critical spatial interaction, compromising protein stability. Functional analyses demonstrate that both de novo variants are pathogenic through distinct mechanisms, implicating aberrant splicing and structural disruption in ADPKD etiology.
本研究确定了两个常染色体显性多囊肾病（ADPKD）的家系，这些多囊肾病是由新的PKD1变异引起的。先证A携带杂合剪接变体（c.9202-16G > A），表现为双侧肾囊肿。miniGENE试验证实，该变异导致60个碱基切除的异常剪接，导致移码和预测的截断蛋白。先证者B携带错义变异（C .2180 T > C; p.Leu727Pro），表现为多囊肾和肝脏疾病。结构模型显示，这种变异严重破坏了局部二级结构和关键的空间相互作用，损害了蛋白质的稳定性。功能分析表明，这两种新生变异通过不同的机制致病，暗示了ADPKD病因中的异常剪接和结构破坏。
{"title":"De novo PKD1 splicing and missense variants in two familial ADPKD: Molecular characterization and genetic counseling implications","authors":"Juan Zhu , Zi-yan Xu , Hong-ping Yu , Ruo-li Wang , Yi-jia Luo , Li-jun Xie , Jian-hui Zhang , Qian Chen , Peng-fei Wang , Dan-dan Ruan , Jing Zou , Yan-feng Zhou , Li Chen , Fang-meng Huang , Mei-zhu Gao , Li Zhang , Yun-fei Li , Zhu-ting Fang , Li-sheng Liao , Xi-kui Zhang , Zhi-hai Zheng","doi":"10.1016/j.gene.2025.149902","DOIUrl":"10.1016/j.gene.2025.149902","url":null,"abstract":"<div><div>This study identifies two pedigrees with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo PKD1 variants. Proband A carried a heterozygous splicing variant (c.9202-16G > A), presenting with bilateral renal cysts. The miniGENE assay confirmed this variant causes aberrant splicing with a 60-base excision, leading to a frameshift and a predicted truncated protein. Proband B carried a missense variant (c.2180 T > C; p.Leu727Pro), presenting with polycystic kidney and liver disease. Structural modeling revealed this variant severely disrupts local secondary structure and a critical spatial interaction, compromising protein stability. Functional analyses demonstrate that both de novo variants are pathogenic through distinct mechanisms, implicating aberrant splicing and structural disruption in ADPKD etiology.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149902"},"PeriodicalIF":2.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534407","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}
Pub Date : 2025-11-13DOI: 10.1016/j.gene.2025.149893
Rosyely da Silva Oliveira , Nilson César Oliveira Alves Filho , Walter de Barros Gomes Netto , Denis de Castro Silva , Mônica Silva de Oliveira , Ana Carolina Favacho Miranda de Oliveira , Rafael Azevedo Baraúna , Diego Assis das Graças , Artur Silva , Adonney Allan de Oliveira Veras
To determine the gene content of an organism, the reads generated by the sequencing process must be assembled using an assembly strategy, either by reference or de novo. However, this process often results in multiple sequences called contigs, which, after the sorting steps, are grouped into scaffolds. The completion stage aims to obtain a single genomic sequence, called a complete genome, which is not a trivial task. Various analytical strategies have been developed to help in this process, many of which have been implemented in computer tools to obtain complete genomes or as close to this as possible, the so-called drafts. The manuscript presents ContigPolishing, a computational tool with a simple and intuitive graphical interface, developed to improve the assembly of prokaryotic genomes, such as bacteria and metagenomes. Despite existing software, there is a gap for solutions that combine simplicity and robustness. ContigPolishing addresses this need, featuring an integrated database that allows processing to be resumed at any time. The tool was validated with 90 NCBI datasets from genera such as Escherichia coli, Corynebacterium, and Nocardia, as well as raw reads from the SRA database to simulate real-world situations. The results showed improvement in the contiguity of the assemblies, with an increase in N50 and improvement in L50, and a reduction in the number of contigs, by extending the contigs using the similarity between their flanks. In some cases, the software was able to elevate the status of genomes from draft to complete, proving its efficiency. ContigPolishing is available at: https://github.com/allanverasce/contigpolishing.
{"title":"ContigPolishing: A User-Friendly Java GUI for contig extension and refinement in prokaryotic genomes","authors":"Rosyely da Silva Oliveira , Nilson César Oliveira Alves Filho , Walter de Barros Gomes Netto , Denis de Castro Silva , Mônica Silva de Oliveira , Ana Carolina Favacho Miranda de Oliveira , Rafael Azevedo Baraúna , Diego Assis das Graças , Artur Silva , Adonney Allan de Oliveira Veras","doi":"10.1016/j.gene.2025.149893","DOIUrl":"10.1016/j.gene.2025.149893","url":null,"abstract":"<div><div>To determine the gene content of an organism, the reads generated by the sequencing process must be assembled using an assembly strategy, either by reference or de novo. However, this process often results in multiple sequences called contigs, which, after the sorting steps, are grouped into scaffolds. The completion stage aims to obtain a single genomic sequence, called a complete genome, which is not a trivial task. Various analytical strategies have been developed to help in this process, many of which have been implemented in computer tools to obtain complete genomes or as close to this as possible, the so-called drafts. The manuscript presents ContigPolishing, a computational tool with a simple and intuitive graphical interface, developed to improve the assembly of prokaryotic genomes, such as bacteria and metagenomes. Despite existing software, there is a gap for solutions that combine simplicity and robustness. ContigPolishing addresses this need, featuring an integrated database that allows processing to be resumed at any time. The tool was validated with 90 NCBI datasets from genera such as Escherichia coli, Corynebacterium, and Nocardia, as well as raw reads from the SRA database to simulate real-world situations. The results showed improvement in the contiguity of the assemblies, with an increase in N50 and improvement in L50, and a reduction in the number of contigs, by extending the contigs using the similarity between their flanks. In some cases, the software was able to elevate the status of genomes from draft to complete, proving its efficiency. ContigPolishing is available at: <span><span>https://github.com/allanverasce/contigpolishing</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149893"},"PeriodicalIF":2.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523192","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}
Pub Date : 2025-11-12DOI: 10.1016/j.gene.2025.149894
Diego Garzón-Ospina , Sindy P. Buitrago , Natalia Cepeda-Riaño , Carlos J. Castro-Cavadía , María Fernanda Yasnot-Acosta
Malaria caused by Plasmodium vivax remains a significant public health challenge, with vaccine development hindered by factors such as antigenic diversity and immune evasion. The Cysteine-Rich Protective Antigen (CyRPA), a key protein involved in erythrocyte invasion, has emerged as a promising vaccine candidate. However, its genetic diversity and immunological properties have not been fully explored. This study aimed to analyze the genetic diversity, selective pressures, and antigenic potential of the pvcyrpa locus using 950 sequences, including 42 newly obtained isolates from Colombia. The pvcyrpa gene displayed high nucleotide diversity shaped by both natural selection and recombination. In-silico predictions identified B- and T-cell epitopes, encompassing mainly polymorphic regions, with strong binding affinities predicted for multiple HLA alleles. Notably, these epitopes overlapped with regions previously shown to elicit immune responses in natural infections, as reported in a recent study. Moreover, immune simulation of a multiepitope C-terminal construct predicted a robust humoral memory profile. Collectively, these genetic, epitope-mapping, and immune-simulation findings highlight the conserved C-terminal region of PvCyRPA as a strong, broadly reactive vaccine candidate, providing a rational basis for subsequent in-vitro and in-vivo validation.
{"title":"Genetic diversity, natural selection, and immunological features of the Plasmodium vivax CyRPA protein: Implications for vaccine development","authors":"Diego Garzón-Ospina , Sindy P. Buitrago , Natalia Cepeda-Riaño , Carlos J. Castro-Cavadía , María Fernanda Yasnot-Acosta","doi":"10.1016/j.gene.2025.149894","DOIUrl":"10.1016/j.gene.2025.149894","url":null,"abstract":"<div><div>Malaria caused by <em>Plasmodium vivax</em> remains a significant public health challenge, with vaccine development hindered by factors such as antigenic diversity and immune evasion. The Cysteine-Rich Protective Antigen (CyRPA), a key protein involved in erythrocyte invasion, has emerged as a promising vaccine candidate. However, its genetic diversity and immunological properties have not been fully explored. This study aimed to analyze the genetic diversity, selective pressures, and antigenic potential of the <em>pvcyrpa</em> locus using 950 sequences, including 42 newly obtained isolates from Colombia. The <em>pvcyrpa</em> gene displayed high nucleotide diversity shaped by both natural selection and recombination. <em>In-silico</em> predictions identified B- and T-cell epitopes, encompassing mainly polymorphic regions, with strong binding affinities predicted for multiple HLA alleles. Notably, these epitopes overlapped with regions previously shown to elicit immune responses in natural infections, as reported in a recent study. Moreover, immune simulation of a multiepitope C-terminal construct predicted a robust humoral memory profile. Collectively, these genetic, epitope-mapping, and immune-simulation findings highlight the conserved C-terminal region of PvCyRPA as a strong, broadly reactive vaccine candidate, providing a rational basis for subsequent <em>in-vitro</em> and <em>in-vivo</em> validation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149894"},"PeriodicalIF":2.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523126","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":"Retraction notice to “Association between -251A> T polymorphism in the interleukin-8 gene and oral cancer risk: a meta-analysis.” [Gene 522 (2013) 168–176]","authors":"Zhiming Wang, Chuanning Wang, Zhiguo Zhao, Fang Liu, Xinming Guan, Xiaoping Lin, Liping Zhang","doi":"10.1016/j.gene.2025.149875","DOIUrl":"10.1016/j.gene.2025.149875","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"975 ","pages":"Article 149875"},"PeriodicalIF":2.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503308","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}
Pub Date : 2025-11-11DOI: 10.1016/j.gene.2025.149892
Wei Siang , Wang Guoyun , Feng Yan , Lin Wenji
Sepsis-induced cardiomyopathy (SICM) significantly contributes to sepsis-related mortality, yet its molecular mechanisms remain incompletely understood. Here, we identify cuproptosis—a copper-dependent mitochondrial cell death pathway—as a critical driver of SICM pathogenesis. In a murine SICM model induced by lipopolysaccharide (LPS), cardiac dysfunction was accompanied by myocardial copper accumulation and dysregulation of cuproptosis regulators. RNA sequencing (RNA-seq) analysis revealed cuproptosis as one of the top enriched pathways. Crucially, we demonstrate that the m7G methyltransferase Mettl1 functions as a cardioprotective factor. Mettl1 expression was upregulated in septic hearts and positively correlated with copper levels. In vitro, Mettl1 knockdown exacerbated LPS-induced cytotoxicity in cardiomyocytes and amplified intracellular copper overload. Mechanistically, Mettl1 deficiency potentiated LPS-triggered upregulation of FDX1—a key executor of cuproptosis—and suppressed PDHA1 expression. Our findings establish Mettl1 as a novel suppressor of cuproptosis that confers protection against sepsis-induced cardiotoxicity by restraining FDX1-mediated copper-dependent cell death. Targeting the Mettl1-FDX1 axis may offer a promising therapeutic strategy for SICM.
{"title":"Mettl1 mitigates sepsis-induced cardiomyopathy via inhibition of FDX1-dependent cuproptosis","authors":"Wei Siang , Wang Guoyun , Feng Yan , Lin Wenji","doi":"10.1016/j.gene.2025.149892","DOIUrl":"10.1016/j.gene.2025.149892","url":null,"abstract":"<div><div>Sepsis-induced cardiomyopathy (SICM) significantly contributes to sepsis-related mortality, yet its molecular mechanisms remain incompletely understood. Here, we identify cuproptosis—a copper-dependent mitochondrial cell death pathway—as a critical driver of SICM pathogenesis. In a murine SICM model induced by lipopolysaccharide (LPS), cardiac dysfunction was accompanied by myocardial copper accumulation and dysregulation of cuproptosis regulators. RNA sequencing (RNA-seq) analysis revealed cuproptosis as one of the top enriched pathways. Crucially, we demonstrate that the m7G methyltransferase Mettl1 functions as a cardioprotective factor. Mettl1 expression was upregulated in septic hearts and positively correlated with copper levels. <em>In vitro</em>, Mettl1 knockdown exacerbated LPS-induced cytotoxicity in cardiomyocytes and amplified intracellular copper overload. Mechanistically, Mettl1 deficiency potentiated LPS-triggered upregulation of FDX1—a key executor of cuproptosis—and suppressed PDHA1 expression. Our findings establish Mettl1 as a novel suppressor of cuproptosis that confers protection against sepsis-induced cardiotoxicity by restraining FDX1-mediated copper-dependent cell death. Targeting the Mettl1-FDX1 axis may offer a promising therapeutic strategy for SICM.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149892"},"PeriodicalIF":2.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511585","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}
The miR-302 cluster, a key pluripotency-associated non-coding RNA, has been implicated in stem cell homeostasis and tumourigenesis. However, its regulatory mechanisms in cancers, including colorectal cancer (CRC) remain poorly understood. Here, we demonstrate that the β-catenin/TCF4 complex significantly enhances miR-302 expression through direct promoter activation in CRC cells. We hypothesized that the β-catenin/TCF4 complex directly activates the miR-302 promoter and cooperates with NANOG in a transcriptional feedback loop sustaining stem-like traits in CRC cells. Using a combination of promoter-driven luciferase reporter assays, chromatin immunoprecipitation (ChIP), and molecular dynamics simulations, we identify a regulatory axis involving Wnt signalling and the transcription factor NANOG. Our data show that individual members of the miR-302 cluster activate the NANOG promoter, while both NANOG and β-catenin/TCF4 synergistically enhance miR-302 promoter activity, suggesting the presence of a positive feedback loop. Structural simulations further elucidate the binding interactions between TCF4, NANOG, and the miR-302 promoter, corroborating our experimental observations. Together, these findings position miR-302 as a downstream effector of Wnt/β-catenin signalling and an integral component of NANOG-mediated transcriptional networks in CRC stem-like cells. This work advances our understanding of non-coding RNA regulation in cancer and highlights potential therapeutic opportunities for targeting stemness-associated pathways.
{"title":"β-catenin/TCF4/NANOG axis controls miR-302 transcription in colorectal cancer cells","authors":"Kiarash Saleki , Miao Xue , Amirreza Mazloomi , Bradley Spencer-Dene , Abdolrahman S. Nateri","doi":"10.1016/j.gene.2025.149890","DOIUrl":"10.1016/j.gene.2025.149890","url":null,"abstract":"<div><div>The miR-302 cluster, a key pluripotency-associated non-coding RNA, has been implicated in stem cell homeostasis and tumourigenesis. However, its regulatory mechanisms in cancers, including colorectal cancer (CRC) remain poorly understood. Here, we demonstrate that the β-catenin/TCF4 complex significantly enhances miR-302 expression through direct promoter activation in CRC cells. We hypothesized that the β-catenin/TCF4 complex directly activates the miR-302 promoter and cooperates with NANOG in a transcriptional feedback loop sustaining stem-like traits in CRC cells. Using a combination of promoter-driven luciferase reporter assays, chromatin immunoprecipitation (ChIP), and molecular dynamics simulations, we identify a regulatory axis involving Wnt signalling and the transcription factor NANOG. Our data show that individual members of the miR-302 cluster activate the NANOG promoter, while both NANOG and β-catenin/TCF4 synergistically enhance miR-302 promoter activity, suggesting the presence of a positive feedback loop. Structural simulations further elucidate the binding interactions between TCF4, NANOG, and the miR-302 promoter, corroborating our experimental observations. Together, these findings position miR-302 as a downstream effector of Wnt/β-catenin signalling and an integral component of NANOG-mediated transcriptional networks in CRC stem-like cells. This work advances our understanding of non-coding RNA regulation in cancer and highlights potential therapeutic opportunities for targeting stemness-associated pathways.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149890"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503311","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}
Pub Date : 2025-11-10DOI: 10.1016/j.gene.2025.149877
Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma
China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise FST revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (FROH = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including DCN, SEMA3D, FGF5, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., MTOR, ROBO2, PPP3CA) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.
{"title":"Population structure analysis of eight goat breeds based on super-genotyping-by-sequencing","authors":"Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma","doi":"10.1016/j.gene.2025.149877","DOIUrl":"10.1016/j.gene.2025.149877","url":null,"abstract":"<div><div>China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise <em>F</em><sub>ST</sub> revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (F<sub>ROH</sub> = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including <em>DCN</em>, <em>SEMA3D</em>, <em>FGF5</em>, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., <em>MTOR</em>, <em>ROBO2</em>, <em>PPP3CA</em>) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149877"},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503322","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}
Pub Date : 2025-11-09DOI: 10.1016/j.gene.2025.149889
Zhuangwei Lv , Ruohao Yang , Jinhua Wu , Xiaoyu Shi , Ruihan Wang , Yi’ang Niu , Zhuang Qian , Junna Jiao , Yunfeng Ma
Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα), a core circadian regulator, plays context-dependent dual roles in cancer, acting as either a tumor suppressor or oncogene. This review synthesizes current evidence on NR1D1’s regulation of key oncogenic pathways: DNA repair, immunomodulation (e.g., the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, NOD-like receptor family pyrin domain containing 3(NLRP3)), metabolism, and signaling cascades such as PI3K/AKT, JAK/STAT. We highlight its clinical utility as a prognostic biomarker and therapeutic target, focusing on pharmacological modulators with demonstrated preclinical efficacy. We also critically discuss challenges in targeting NR1D1 and its potential in combination therapies, offering new insights for cancer treatment.
{"title":"NR1D1 in tumorigenesis: dual roles, mechanisms, and therapeutic targeting","authors":"Zhuangwei Lv , Ruohao Yang , Jinhua Wu , Xiaoyu Shi , Ruihan Wang , Yi’ang Niu , Zhuang Qian , Junna Jiao , Yunfeng Ma","doi":"10.1016/j.gene.2025.149889","DOIUrl":"10.1016/j.gene.2025.149889","url":null,"abstract":"<div><div>Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα), a core circadian regulator, plays context-dependent dual roles in cancer, acting as either a tumor suppressor or oncogene. This review synthesizes current evidence on NR1D1’s regulation of key oncogenic pathways: DNA repair, immunomodulation (e.g., the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, NOD-like receptor family pyrin domain containing 3(NLRP3)), metabolism, and signaling cascades such as PI3K/AKT, JAK/STAT. We highlight its clinical utility as a prognostic biomarker and therapeutic target, focusing on pharmacological modulators with demonstrated preclinical efficacy. We also critically discuss challenges in targeting NR1D1 and its potential in combination therapies, offering new insights for cancer treatment.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149889"},"PeriodicalIF":2.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495214","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}
ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.
{"title":"Double minutes: exploring the formation and oncogenic roles in cancer progression","authors":"Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Jahin Fairuj Oishi, Reasat Tarannum, Nusrat Zahan Rouf","doi":"10.1016/j.gene.2025.149879","DOIUrl":"10.1016/j.gene.2025.149879","url":null,"abstract":"<div><div>ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149879"},"PeriodicalIF":2.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487869","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}
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