IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-05 Epub Date: 2025-11-20 DOI: 10.1016/j.gene.2025.149914

Yunwei Zhao, Kaifan Shang, Ping Wang

Pugionium cornutum is a biennial herb belonging to the Brassicaceae family and is an endemic species of the Mongolian Plateau, exhibiting strong stress tolerance and notable medicinal value. In this study, the PcHARBI1-5 gene was cloned from P. cornutum and functionally characterized through heterologous transformation in Arabidopsis thaliana. Transgenic overexpression lines (OE) and homologous knockout mutants (KO-1) were generated, and their phenotypic differences were systematically evaluated under controlled conditions. Overexpression of PcHARBI1-5 significantly promoted early flowering in Arabidopsis, with transgenic plants flowering approximately four days earlier than wild-type controls, whereas the KO-1 mutant exhibited a delay of about three days. Furthermore, transgenic lines displayed enhanced agronomic performance, including longer roots, increased plant height, greater lateral branching, elongated siliques, and higher seed yield per plant. Gene expression analysis revealed that PcHARBI1-5 modulates flowering time by down-regulating the floral repressor FLC and up-regulating key floral integrators FT and SOC1. Taken together, this study reports the successful cloning and functional validation of PcHARBI1-5 from P. cornutum, demonstrating its pivotal role in accelerating flowering and improving multiple agronomic traits. These findings highlight PcHARBI1-5 as a promising candidate gene for molecular breeding strategies aimed at developing early-maturing and high-yielding crop varieties.

Pugionium cornutum是芸苔科二年生草本植物，是蒙古高原的特有种，具有较强的抗逆性和显著的药用价值。本研究从拟南芥中克隆了PcHARBI1-5基因，并通过异源转化对其进行了功能表征。生成转基因过表达系（OE）和同源敲除突变体（KO-1），并在控制条件下系统评价其表型差异。PcHARBI1-5的过表达显著促进了拟南芥的提前开花，转基因植株的开花时间比野生型对照提前了大约4天，而KO-1突变体的开花时间延迟了大约3天。此外，转基因品系表现出更强的农艺性能，包括更长的根、更高的株高、更大的侧分枝、更长的角部和更高的单株种子产量。基因表达分析表明，PcHARBI1-5通过下调花抑制因子FLC和上调关键花整合子FT和SOC1来调节开花时间。综上所述，本研究成功克隆了角草PcHARBI1-5基因，并对其功能进行了验证，证明了其在加速开花和改善多种农艺性状方面的关键作用。这些发现表明PcHARBI1-5是一个有希望的候选基因，用于开发早熟高产作物品种的分子育种策略。

{"title":"Pugionium cornutum PcHARBI1-5 (Harbinger Transposase Derived 1–5) facilitates early flowing and seed development in in Arabidopsis thaliana","authors":"Yunwei Zhao, Kaifan Shang, Ping Wang","doi":"10.1016/j.gene.2025.149914","DOIUrl":"10.1016/j.gene.2025.149914","url":null,"abstract":"<div><div><em>Pugionium cornutum</em> is a biennial herb belonging to the Brassicaceae family and is an endemic species of the Mongolian Plateau, exhibiting strong stress tolerance and notable medicinal value. In this study, the <em>PcHARBI1-5</em> gene was cloned from <em>P. cornutum</em> and functionally characterized through heterologous transformation in <em>Arabidopsis thaliana</em>. Transgenic overexpression lines (OE) and homologous knockout mutants (KO-1) were generated, and their phenotypic differences were systematically evaluated under controlled conditions. Overexpression of <em>PcHARBI1-5</em> significantly promoted early flowering in <em>Arabidopsis</em>, with transgenic plants flowering approximately four days earlier than wild-type controls, whereas the KO-1 mutant exhibited a delay of about three days. Furthermore, transgenic lines displayed enhanced agronomic performance, including longer roots, increased plant height, greater lateral branching, elongated siliques, and higher seed yield per plant. Gene expression analysis revealed that <em>PcHARBI1-5</em> modulates flowering time by down-regulating the floral repressor <em>FLC</em> and up-regulating key floral integrators <em>FT</em> and <em>SOC1</em>. Taken together, this study reports the successful cloning and functional validation of <em>PcHARBI1-5</em> from <em>P. cornutum</em>, demonstrating its pivotal role in accelerating flowering and improving multiple agronomic traits. These findings highlight <em>PcHARBI1-5</em> as a promising candidate gene for molecular breeding strategies aimed at developing early-maturing and high-yielding crop varieties.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149914"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577704","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}

引用次数: 0

De novo PKD1 splicing and missense variants in two familial ADPKD: Molecular characterization and genetic counseling implications 两个家族性ADPKD的新生PKD1剪接和错义变异：分子表征和遗传咨询意义。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-05 Epub Date: 2025-11-14 DOI: 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":"2026-02-05","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}

引用次数: 0

Revealing the genetic blueprint: A transcriptomic approach to deciphering blue iris color formation in Nili-Ravi buffalo 揭示遗传蓝图：一种转录组学方法来破译Nili-Ravi水牛蓝色虹膜颜色的形成。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-05 Epub Date: 2025-11-06 DOI: 10.1016/j.gene.2025.149878

Dong Wang , Yixue Xu , Chaobin Qin , Xinhui Song , Hui Li , Xiaoxian Xu , Muhammad Farhan Khan , Kuiqing Cui , Zhipeng Li , Qingyou Liu

Water buffalo are economically significant livestock worldwide, yet the genetic basis of the blue iris in Nili-Ravi buffalo remains elusive. We collected mixed iris–lens samples from two Murrah buffaloes (black iris) and two Nili-Ravi buffaloes (blue iris) and performed paired-end RNA-seq. After quality control, 64.53 Gb of high-quality data (Q30 ≥ 89.92 %) were obtained. Differential analysis (DESeq2,|log₂FoldChange| ≥ 2 and padj < 0.05) revealed 1,289 differentially expressed genes and 248 differentially expressed lncRNAs between blue and black irises. GO and KEGG enrichment highlighted melanogenesis, tyrosine metabolism, cysteine metabolism, and phototransduction pathways. Key differential genes related to eye development and melanin production—including the hub mRNAs KIT, MGST1, GNGT1, and TYRP1—were identified. Network analysis further showed that lncRNA MSTRG.14079.1 directly targets protein tyrosine phosphatase receptor T (PTPRT), and this interaction is significantly down-regulated in blue irises. Together, our study provides the first molecular network underlying the blue iris phenotype and establishes a theoretical basis for using this non-invasive marker to enhance breeding efficiency in buffalo.

水牛是世界范围内具有重要经济意义的牲畜，但尼利-拉维水牛蓝虹膜的遗传基础仍然难以捉摸。我们采集了两只Murrah水牛（黑色虹膜）和两只Nili-Ravi水牛（蓝色虹膜）的混合虹膜透镜样本，并进行了对端rna测序。经质量控制，获得高质量数据64.53 Gb （Q30 ≥ 89.92 %）。差异分析(DESeq2， | log2FoldChange |≥2和padj

{"title":"Revealing the genetic blueprint: A transcriptomic approach to deciphering blue iris color formation in Nili-Ravi buffalo","authors":"Dong Wang , Yixue Xu , Chaobin Qin , Xinhui Song , Hui Li , Xiaoxian Xu , Muhammad Farhan Khan , Kuiqing Cui , Zhipeng Li , Qingyou Liu","doi":"10.1016/j.gene.2025.149878","DOIUrl":"10.1016/j.gene.2025.149878","url":null,"abstract":"<div><div>Water buffalo are economically significant livestock worldwide, yet the genetic basis of the blue iris in Nili-Ravi buffalo remains elusive. We collected mixed iris–lens samples from two Murrah buffaloes (black iris) and two Nili-Ravi buffaloes (blue iris) and performed paired-end RNA-seq. After quality control, 64.53 Gb of high-quality data (Q30 ≥ 89.92 %) were obtained. Differential analysis (DESeq2,|log<sub>2</sub>FoldChange| ≥ 2 and padj < 0.05) revealed 1,289 differentially expressed genes and 248 differentially expressed lncRNAs between blue and black irises. GO and KEGG enrichment highlighted melanogenesis, tyrosine metabolism, cysteine metabolism, and phototransduction pathways. Key differential genes related to eye development and melanin production—including the hub mRNAs <em>KIT</em>, <em>MGST1</em>, <em>GNGT1</em>, and <em>TYRP1</em>—were identified. Network analysis further showed that lncRNA MSTRG.14079.1 directly targets protein tyrosine phosphatase receptor T (<em>PTPRT</em>), and this interaction is significantly down-regulated in blue irises. Together, our study provides the first molecular network underlying the blue iris phenotype and establishes a theoretical basis for using this non-invasive marker to enhance breeding efficiency in buffalo.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149878"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476871","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}

引用次数: 0

Genetic diversity, natural selection, and immunological features of the Plasmodium vivax CyRPA protein: Implications for vaccine development 间日疟原虫CyRPA蛋白的遗传多样性、自然选择和免疫学特征：对疫苗开发的影响。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-05 Epub Date: 2025-11-12 DOI: 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.

间日疟原虫引起的疟疾仍然是一个重大的公共卫生挑战，疫苗的开发受到抗原多样性和免疫逃避等因素的阻碍。富含半胱氨酸保护性抗原（CyRPA）是参与红细胞侵袭的关键蛋白，已成为一种有希望的候选疫苗。然而，其遗传多样性和免疫学特性尚未得到充分的研究。本研究利用哥伦比亚新获得的42株pvcyrpa菌株的950个序列，分析了pvcyrpa基因座的遗传多样性、选择压力和抗原性。pvcyrpa基因在自然选择和重组的双重作用下表现出高度的核苷酸多样性。计算机预测确定了B细胞和t细胞表位，主要包括多态性区域，预测多个HLA等位基因具有很强的结合亲和力。值得注意的是，在最近的一项研究中，这些表位与先前显示的在自然感染中引起免疫反应的区域重叠。此外，多表位c末端构建的免疫模拟预测了强大的体液记忆谱。总的来说，这些遗传、表位定位和免疫模拟的发现突出了PvCyRPA的保守c端区域是一个强大的、广泛反应性的候选疫苗，为随后的体外和体内验证提供了合理的基础。

{"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":"2026-02-05","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}

引用次数: 0

Mettl1 mitigates sepsis-induced cardiomyopathy via inhibition of FDX1-dependent cuproptosis Mettl1通过抑制fdx1依赖性铜体增生减轻败血症引起的心肌病。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-05 Epub Date: 2025-11-11 DOI: 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.

败血症性心肌病（SICM）是导致败血症相关死亡率的重要因素，但其分子机制尚不完全清楚。在这里，我们发现铜细胞凋亡——一种依赖铜的线粒体细胞死亡途径——是SICM发病机制的一个关键驱动因素。在脂多糖（LPS）诱导的小鼠SICM模型中，心功能障碍伴随着心肌铜积累和铜增生调节因子的失调。RNA测序（RNA-seq）分析显示cuprotosis是最富集的途径之一。至关重要的是，我们证明了m7G甲基转移酶Mettl1作为一种心脏保护因子发挥作用。Mettl1在脓毒症心脏中表达上调，且与铜水平呈正相关。在体外，Mettl1敲低加剧了lps诱导的心肌细胞毒性，并放大了细胞内铜超载。从机制上讲，Mettl1缺乏增强了lps触发的fdx1（铜生长的关键执行者）的上调，并抑制了PDHA1的表达。我们的研究结果表明，Mettl1是一种新的铜增生抑制因子，通过抑制fdx1介导的铜依赖性细胞死亡，可以防止败血症诱导的心脏毒性。靶向Mettl1-FDX1轴可能为SICM提供一种有希望的治疗策略。

{"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":"2026-02-05","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}

引用次数: 0

Study on the molecular mechanism of dietary FCE supplementation in regulating chicken meat quality 饲粮中添加FCE调节鸡肉品质的分子机制研究。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-20 Epub Date: 2025-10-30 DOI: 10.1016/j.gene.2025.149865

Wei Zhao, Jinli Tian, Lijuan Yang, Lin Xue, Siyu Chen, Rinmin Ma, Yaling Gu, Dawei Wei, Juan Zhang

Meat quality is a critical factor influencing the sales of chicken. Most plant extracts have been shown to improve meat quality in poultry. This study selected 120 similar-weight (1.5 ± 0.2 kg) 135-day-old Jingyuan chickens, divided them into four groups, and fed them different doses (CON, 0.3 % FCE, 0.6 % FCE, and 0.9 % FCE) of fresh corn extract (FCE) until they were 180-day-old chickens. Fifteen chickens were randomly selected from each group for slaughter performance and meat quality assessment. Combining the transcriptome and metabolome sequencing data of the breast (CON and 0.6 % FCE), the weighted co-expression network analysis (WGCNA) method was used to identify hub genes and key metabolites significantly related to meat quality. The results showed that the 0.6 % FCE group was significantly better than the other groups in terms of slaughter performance and meat quality. Transcriptomic analysis identified differentially expressed genes (DEGs) significantly enriched in mineral absorption, amino sugar and nucleotide sugar metabolism, and phosphonate and phosphinate metabolism. Based on WGCNA, six key DEGs significantly associated with meat quality were selected. Metabolomics analysis identified differentially expressed metabolites (DEMs) significantly enriched in the pathways of secondary bile acid biosynthesis, autophagy, pantothenate and CoA biosynthesis, and beta-alanine metabolism Pearson correlation analysis further revealed correlations between the six key DEGs (YKT6, ENSGALG00010016848, GALK2, COMMD9, EIF2D, and GABPB2) and five key DEMs (1H-Indole-4-carboxaldehyde, Leucylproline, Trimethoprim, Ursodeoxycholic acid, and N.epsilon.-Acetyl-L-lysine). Furthermore, the expression levels and content of these genes and metabolites in the breast muscle of Jingyuan chickens were also assessed.

肉质是影响鸡肉销售的关键因素。大多数植物提取物已被证明能改善家禽的肉质。本试验选取体重相近（1.5 ± 0.2 kg）的135日龄靖远鸡120只，分为4组，分别饲喂不同剂量（CON、0.3 % FCE、0.6 % FCE和0.9 % FCE）的新鲜玉米提取物（FCE）至180日龄。每组随机选取15只鸡进行屠宰性能和肉质评价。结合乳腺转录组和代谢组测序数据（CON和0.6 % FCE），采用加权共表达网络分析（WGCNA）方法，鉴定与肉品质显著相关的枢纽基因和关键代谢物。结果表明，0.6 % FCE组屠宰性能和肉质均显著优于其他各组。转录组学分析发现，差异表达基因（DEGs）在矿物质吸收、氨基糖和核苷酸糖代谢、磷酸盐和膦酸盐代谢中显著富集。基于WGCNA，选择了6个与肉质性状显著相关的关键deg。代谢组学分析发现，在次生胆囊酸生物合成、自噬、泛酸和辅酶a生物合成途径中显著富集的差异表达代谢物（DEMs）， β -丙氨酸代谢Pearson相关分析进一步揭示了6个关键DEGs （YKT6、ENSGALG00010016848、GALK2、COMMD9、EIF2D和GABPB2）与5个关键DEMs (1h -吲哚-4-甲醛、Leucylproline、Trimethoprim、Ursodeoxycholic acid、和N.epsilon.-Acetyl-L-lysine)。此外，还对这些基因和代谢物在靖远鸡胸肌中的表达水平和含量进行了评价。

{"title":"Study on the molecular mechanism of dietary FCE supplementation in regulating chicken meat quality","authors":"Wei Zhao, Jinli Tian, Lijuan Yang, Lin Xue, Siyu Chen, Rinmin Ma, Yaling Gu, Dawei Wei, Juan Zhang","doi":"10.1016/j.gene.2025.149865","DOIUrl":"10.1016/j.gene.2025.149865","url":null,"abstract":"<div><div>Meat quality is a critical factor influencing the sales of chicken. Most plant extracts have been shown to improve meat quality in poultry. This study selected 120 similar-weight (1.5 ± 0.2 kg) 135-day-old Jingyuan chickens, divided them into four groups, and fed them different doses (CON, 0.3 % FCE, 0.6 % FCE, and 0.9 % FCE) of fresh corn extract (FCE) until they were 180-day-old chickens. Fifteen chickens were randomly selected from each group for slaughter performance and meat quality assessment. Combining the transcriptome and metabolome sequencing data of the breast (CON and 0.6 % FCE), the weighted co-expression network analysis (WGCNA) method was used to identify hub genes and key metabolites significantly related to meat quality. The results showed that the 0.6 % FCE group was significantly better than the other groups in terms of slaughter performance and meat quality. Transcriptomic analysis identified differentially expressed genes (DEGs) significantly enriched in mineral absorption, amino sugar and nucleotide sugar metabolism, and phosphonate and phosphinate metabolism. Based on WGCNA, six key DEGs significantly associated with meat quality were selected. Metabolomics analysis identified differentially expressed metabolites (DEMs) significantly enriched in the pathways of secondary bile acid biosynthesis, autophagy, pantothenate and CoA biosynthesis, and beta-alanine metabolism Pearson correlation analysis further revealed correlations between the six key DEGs (<em>YKT6</em>, <em>ENSGALG00010016848</em>, <em>GALK2</em>, <em>COMMD9</em>, <em>EIF2D</em>, and <em>GABPB2</em>) and five key DEMs (1H-Indole-4-carboxaldehyde, Leucylproline, Trimethoprim, Ursodeoxycholic acid, and N.epsilon.-Acetyl-L-lysine). Furthermore, the expression levels and content of these genes and metabolites in the breast muscle of Jingyuan chickens were also assessed.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149865"},"PeriodicalIF":2.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421732","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}

引用次数: 0

Expression analysis of androglobin and its influence on the transcriptome in cancer 雄性红蛋白在肿瘤组织中的表达分析及其对转录组的影响。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-20 Epub Date: 2025-10-24 DOI: 10.1016/j.gene.2025.149840

Carina Osterhof , Michel Seiwert , Stefan Mündnich , Teng Wei Koay , Elena Porto , Glen Kristiansen , David Hoogewijs , Thomas Hankeln

Androglobin (ADGB) is a phylogenetically ancient multi-domain protein with an embedded globin domain, which binds heme and may therefore interact with gaseous molecules. Other globins like neuroglobin, cytoglobin and myoglobin have shown tumor-suppressor or oncogenic roles in a tissue-dependent way, and also ADGB has been suggested as being oncogenic in prostate and brain cancer models. However, ADGB expression in human tumor entities in vivo has not been investigated systematically so far. Here we mined transcriptome data from various cancer types and reveal that ADGB is typically downregulated in cancer cell lines, as well as in tumors from lung and testis, which express ADGB endogenously in healthy states. We show via bioinformatics analyses that in cell lines only a few ADGB exons are transcribed, or the gene locus was amplified, which greatly limits suitability of such cell lines as model systems for research into ADGB. Consistent with correlation analysis, we further demonstrate that RFX3 regulates ADGB promoter-driven luciferase activity as well as endogenous ADGB expression levels. Since recent literature postulated oncogenic effects of ADGB, we established stable ADGB overexpression (ADGB+) in A549 lung cancer cells. Our transcriptomic analysis of ADGB + cells indicate increased cell motility and restructuring of the extracellular matrix – both hallmarks of elevated malignancy. ADGB thus may display oncogenic potential in vitro. However, since human cancer entities show little to no ADGB transcription, a role for ADGB in tumorigenesis in vivo appears rather limited.

Androglobin （ADGB）是一种具有嵌入式珠蛋白结构域的古老多结构域蛋白，与血红素结合，因此可能与气体分子相互作用。其他珠蛋白如神经珠蛋白、细胞珠蛋白和肌红蛋白以组织依赖的方式显示出肿瘤抑制或致癌作用，ADGB也被认为在前列腺癌和脑癌模型中具有致癌作用。然而，到目前为止，ADGB在人体肿瘤实体中的表达还没有系统的研究。在这里，我们挖掘了来自各种癌症类型的转录组数据，发现ADGB在癌细胞系以及肺和睾丸肿瘤中通常是下调的，这些肿瘤在健康状态下内源性表达ADGB。我们通过生物信息学分析表明，在细胞系中，只有少数ADGB外显子被转录，或者基因位点被扩增，这极大地限制了这些细胞系作为ADGB研究模型系统的适用性。与相关分析一致，我们进一步证明RFX3调节ADGB启动子驱动的荧光素酶活性以及内源性ADGB表达水平。由于最近的文献假设了ADGB的致癌作用，我们在A549肺癌细胞中建立了稳定的ADGB过表达（ADGB + ）。我们对ADGB + 细胞的转录组学分析表明，细胞运动性和细胞外基质的重组增加，这两者都是恶性肿瘤升高的标志。因此，ADGB在体外可能显示出致癌潜力。然而，由于人类癌症实体很少或没有ADGB转录，ADGB在体内肿瘤发生中的作用似乎相当有限。

{"title":"Expression analysis of androglobin and its influence on the transcriptome in cancer","authors":"Carina Osterhof , Michel Seiwert , Stefan Mündnich , Teng Wei Koay , Elena Porto , Glen Kristiansen , David Hoogewijs , Thomas Hankeln","doi":"10.1016/j.gene.2025.149840","DOIUrl":"10.1016/j.gene.2025.149840","url":null,"abstract":"<div><div>Androglobin (ADGB) is a phylogenetically ancient multi-domain protein with an embedded globin domain, which binds heme and may therefore interact with gaseous molecules. Other globins like neuroglobin, cytoglobin and myoglobin have shown tumor-suppressor or oncogenic roles in a tissue-dependent way, and also ADGB has been suggested as being oncogenic in prostate and brain cancer models. However, <em>ADGB</em> expression in human tumor entities <em>in vivo</em> has not been investigated systematically so far. Here we mined transcriptome data from various cancer types and reveal that <em>ADGB</em> is typically downregulated in cancer cell lines, as well as in tumors from lung and testis, which express <em>ADGB</em> endogenously in healthy states. We show via bioinformatics analyses that in cell lines only a few <em>ADGB</em> exons are transcribed, or the gene locus was amplified, which greatly limits suitability of such cell lines as model systems for research into ADGB. Consistent with correlation analysis, we further demonstrate that RFX3 regulates <em>ADGB</em> promoter-driven luciferase activity as well as endogenous <em>ADGB</em> expression levels. Since recent literature postulated oncogenic effects of ADGB, we established stable <em>ADGB</em> overexpression (ADGB+) in A549 lung cancer cells. Our transcriptomic analysis of ADGB + cells indicate increased cell motility and restructuring of the extracellular matrix – both hallmarks of elevated malignancy. ADGB thus may display oncogenic potential <em>in vitro</em>. However, since human cancer entities show little to no <em>ADGB</em> transcription, a role for ADGB in tumorigenesis <em>in vivo</em> appears rather limited.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149840"},"PeriodicalIF":2.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370337","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}

引用次数: 0

β-catenin/TCF4/NANOG axis controls miR-302 transcription in colorectal cancer cells β-catenin/TCF4/NANOG轴控制结直肠癌细胞中miR-302的转录。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-20 Epub Date: 2025-11-10 DOI: 10.1016/j.gene.2025.149890

Kiarash Saleki , Miao Xue , Amirreza Mazloomi , Bradley Spencer-Dene , Abdolrahman S. Nateri

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.

miR-302簇是一种关键的多能性相关非编码RNA，与干细胞稳态和肿瘤发生有关。然而，其在包括结直肠癌（CRC）在内的癌症中的调节机制仍然知之甚少。在这里，我们证明β-catenin/TCF4复合物通过直接启动子激活在CRC细胞中显著增强miR-302的表达。我们假设β-catenin/TCF4复合物直接激活miR-302启动子，并在维持CRC细胞干样性状的转录反馈回路中与NANOG合作。通过结合启动子驱动的荧光素酶报告子测定、染色质免疫沉淀（ChIP）和分子动力学模拟，我们确定了一个涉及Wnt信号和转录因子NANOG的调控轴。我们的数据显示，miR-302集群的单个成员激活NANOG启动子，而NANOG和β-catenin/TCF4协同增强miR-302启动子活性，表明存在正反馈回路。结构模拟进一步阐明了TCF4、NANOG和miR-302启动子之间的结合相互作用，证实了我们的实验观察。总之，这些发现表明miR-302是Wnt/β-catenin信号传导的下游效应因子，也是CRC干细胞样细胞中nanog介导的转录网络的一个组成部分。这项工作促进了我们对癌症中非编码RNA调控的理解，并强调了针对干细胞相关途径的潜在治疗机会。

{"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":"2026-01-20","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}

引用次数: 0

Functional analysis of two component signaling system in Mycobacterium tuberculosis 结核分枝杆菌双组分信号系统的功能分析。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-20 Epub Date: 2025-11-07 DOI: 10.1016/j.gene.2025.149868

Karthikeyan Sundaram , Sridhar Rathinam

Tuberculosis is a fatal infection transmitted through airborne droplet nuclei. The etiological agent is Mycobacterium tuberculosis, an acid-fast bacillus. Drug-resistant tuberculosis poses a global challenge, with specific mycobacterial genes intricately associated with drug resistance. Numerous factors are implicated in the etiology of the condition. This review specifically aims to examine ClpCP, an ATPase belonging to the AAA + protease family, and the genes of the two-component sensor system related with disease etiology. Mycobacterium TB depends significantly on protein degradation to regulate their quantity and quality, which is crucial for its proliferation and pathogenicity involving Clp. The two-component sensor system comprises histidine kinase (HK) and response regulator (RR), which governs responses to stress situations, starvation, nutritional abundance, persistence, hypoxia, dormancy, and primarily disease pathogenesis. Within the two-component system, there exist 12 pairs, including SenX3/RegX3, PhoP/PhoR, DosR/DosS, MtrA/MtrB, and PdtaS/PdtaR, alongside 6 response regulators Rv0195, Rv0260c, Rv0818, PdtaR, Rv2884, and Rv3143 encoded in the Mycobacterium tuberculosis genome. The PhoPR genes have been extensively researched, and the pathogenicity of Mycobacterium tuberculosis (MTB) is contingent upon the sensor kinase of the PhoPR two-component regulatory system, known as PhoR. This review will examine the roles of genes related to the factors associated with mycobacterial growth and pathogenesis.

结核病是一种通过空气传播的飞沫核传播的致命传染病。病原是结核分枝杆菌，一种抗酸杆菌。耐药结核病是一项全球性挑战，特定的分枝杆菌基因与耐药有着错综复杂的关系。许多因素涉及到该病的病因学。这篇综述特别旨在研究ClpCP，一种属于AAA + 蛋白酶家族的atp酶，以及与疾病病因相关的双组分传感器系统基因。结核分枝杆菌主要依靠蛋白质降解来调节其数量和质量，这对其涉及Clp的增殖和致病性至关重要。这种双组分传感器系统包括组氨酸激酶（HK）和反应调节因子（RR），它们控制对应激情况、饥饿、营养丰富、持久性、缺氧、休眠和主要疾病发病机制的反应。在双组分体系中，共编码SenX3/RegX3、PhoP/PhoR、DosR/DosS、MtrA/MtrB、PdtaS/PdtaR等12对，以及Rv0195、Rv0260c、Rv0818、PdtaR、Rv2884、Rv3143 6个应答调控因子。PhoPR基因已被广泛研究，结核分枝杆菌（MTB）的致病性取决于PhoPR双组分调控系统（PhoR）的传感器激酶。本文将探讨与分枝杆菌生长和发病相关的基因的作用。

{"title":"Functional analysis of two component signaling system in Mycobacterium tuberculosis","authors":"Karthikeyan Sundaram , Sridhar Rathinam","doi":"10.1016/j.gene.2025.149868","DOIUrl":"10.1016/j.gene.2025.149868","url":null,"abstract":"<div><div>Tuberculosis is a fatal infection transmitted through airborne droplet nuclei. The etiological agent is Mycobacterium tuberculosis, an acid-fast bacillus. Drug-resistant tuberculosis poses a global challenge, with specific mycobacterial genes intricately associated with drug resistance. Numerous factors are implicated in the etiology of the condition. This review specifically aims to examine ClpCP, an ATPase belonging to the AAA + protease family, and the genes of the two-component sensor system related with disease etiology. Mycobacterium TB depends significantly on protein degradation to regulate their quantity and quality, which is crucial for its proliferation and pathogenicity involving Clp. The two-component sensor system comprises histidine kinase (HK) and response regulator (RR), which governs responses to stress situations, starvation, nutritional abundance, persistence, hypoxia, dormancy, and primarily disease pathogenesis. Within the two-component system, there exist 12 pairs, including SenX3/RegX3, PhoP/PhoR, DosR/DosS, MtrA/MtrB, and PdtaS/PdtaR, alongside 6 response regulators Rv0195, Rv0260c, Rv0818, PdtaR, Rv2884, and Rv3143 encoded in the Mycobacterium tuberculosis genome. The PhoPR genes have been extensively researched, and the pathogenicity of Mycobacterium tuberculosis (MTB) is contingent upon the sensor kinase of the PhoPR two-component regulatory system, known as PhoR. This review will examine the roles of genes related to the factors associated with mycobacterial growth and pathogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149868"},"PeriodicalIF":2.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476837","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}

引用次数: 0

Role of myocardium-derived exosomal miRNAs in doxorubicin-induced cardiomyopathy 心肌源性外泌体mirna在阿霉素诱导的心肌病中的作用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-20 Epub Date: 2025-10-20 DOI: 10.1016/j.gene.2025.149842

Cui Li , Yudie Song , Binbin Cao , Jiahui Li , Fan Xu , Weiping Du , Zhaoxia Zhang , Binjie Su , Xiaomin Chen , Qinglin Yu , Jia Su

Background

Doxorubicin-induced cardiomyopathy (DCM) remains a major clinical challenge, highlighting the need for early diagnostic biomarkers. Exosomal miRNAs are promising candidates due to their stability and regulatory functions in cardiovascular diseases.

Methods

Exosomes were isolated from myocardial tissue samples of DOX-treated and control rats using differential ultracentrifugation and were subsequently characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Differentially expressed miRNAs were screened by microarray analysis. The miRanda algorithm was used to predict target genes, followed by functional enrichment analysis. qRT‒PCR validated selected miRNAs and their target genes.

Results

Doxorubicin administration induced significant cardiac dysfunction, characterized by decreased left ventricular ejection fraction (LVEF) and increased serum levels of cardiac biomarkers (cTnI, BNP, and CK-MB). Microarray profiling revealed 26 differentially expressed miRNAs, and KEGG enrichment analysis indicated enrichment in the MAPK signaling pathway. qRT‒PCR demonstrated upregulation of exosomal miR-182 and downregulation of Taok2 mRNA, a key MAPK gene. ROC analysis indicated the potential of exosomal miR-182 for DCM diagnosis.

Conclusion

Exosomal miR-182 may serve as a diagnostic marker for DCM. Bioinformatic analyses predict its potential regulation of the MAPK pathway through Taok2 targeting, although this mechanistic relationship requires experimental validation. These findings provide new perspectives for the early monitoring of DCM.

背景：阿霉素诱导的心肌病（DCM）仍然是一个主要的临床挑战，突出了对早期诊断生物标志物的需求。外泌体mirna因其在心血管疾病中的稳定性和调节作用而成为有希望的候选者。方法：采用差示超离心方法从dox处理和对照大鼠心肌组织样本中分离外泌体，随后采用透射电镜（TEM）、免疫印迹（Western blotting）和纳米颗粒跟踪分析（NTA）对其进行表征。通过微阵列分析筛选差异表达的mirna。使用miRanda算法预测目标基因，然后进行功能富集分析。qRT-PCR验证了所选的mirna及其靶基因。结果：阿霉素引起了明显的心功能障碍，其特征是左心室射血分数（LVEF）降低，血清心脏生物标志物（cTnI、BNP和CK-MB）水平升高。微阵列分析显示了26个差异表达的mirna， KEGG富集分析表明在MAPK信号通路中富集。qRT-PCR显示外泌体miR-182上调，MAPK关键基因Taok2 mRNA下调。ROC分析显示外泌体miR-182诊断DCM的潜力。结论：外泌体miR-182可作为DCM的诊断标志物。生物信息学分析预测其可能通过Taok2靶向调控MAPK通路，尽管这种机制关系需要实验验证。这些发现为DCM的早期监测提供了新的视角。

{"title":"Role of myocardium-derived exosomal miRNAs in doxorubicin-induced cardiomyopathy","authors":"Cui Li , Yudie Song , Binbin Cao , Jiahui Li , Fan Xu , Weiping Du , Zhaoxia Zhang , Binjie Su , Xiaomin Chen , Qinglin Yu , Jia Su","doi":"10.1016/j.gene.2025.149842","DOIUrl":"10.1016/j.gene.2025.149842","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin-induced cardiomyopathy (DCM) remains a major clinical challenge, highlighting the need for early diagnostic biomarkers. Exosomal miRNAs are promising candidates due to their stability and regulatory functions in cardiovascular diseases.</div></div><div><h3>Methods</h3><div>Exosomes were isolated from myocardial tissue samples of DOX-treated and control rats using differential ultracentrifugation and were subsequently characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Differentially expressed miRNAs were screened by microarray analysis. The miRanda algorithm was used to predict target genes, followed by functional enrichment analysis. qRT‒PCR validated selected miRNAs and their target genes.</div></div><div><h3>Results</h3><div>Doxorubicin administration induced significant cardiac dysfunction, characterized by decreased left ventricular ejection fraction (LVEF) and increased serum levels of cardiac biomarkers (cTnI, BNP, and CK-MB). Microarray profiling revealed 26 differentially expressed miRNAs, and KEGG enrichment analysis indicated enrichment in the MAPK signaling pathway. qRT‒PCR demonstrated upregulation of exosomal miR-182 and downregulation of Taok2 mRNA, a key MAPK gene. ROC analysis indicated the potential of exosomal miR-182 for DCM diagnosis.</div></div><div><h3>Conclusion</h3><div>Exosomal miR-182 may serve as a diagnostic marker for DCM. Bioinformatic analyses predict its potential regulation of the MAPK pathway through Taok2 targeting, although this mechanistic relationship requires experimental validation. These findings provide new perspectives for the early monitoring of DCM.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149842"},"PeriodicalIF":2.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336825","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}

引用次数: 0

Gene最新文献

Background

Methods

Results

Conclusion