Pub Date : 2025-11-27DOI: 10.1016/j.ygeno.2025.111163
Jiawei Chen , Fan Tang , Sichen Bao , Zhuqi Gao , Hong Chen , Qichuan Zhuge , Jianjing Yang , Ying Zhang
Glioma, one of the most common types of primary brain tumors, presents considerable challenges due to its poor prognosis. Emerging research has demonstrated a strong connection between Centromere Protein M(CENPM) and tumor progression. However, the precise role of CENPM in glioma remains poorly understood. This study delves into the involvement of CENPM in glioma progression. Data analysis revealed that heightened CENPM expression correlates with worse patient outcomes and is highly expressed in glioma. In vitro experiments showed that reducing CENPM expression inhibits glioma cell proliferation and induces G0/G1 phase cell cycle arrest. Furthermore, RNA-seq and Western Blot analyses demonstrated that CENPM activates the PI3K/AKT signaling pathway in glioma cells. In vivo experiments confirmed that knocking down CENPM leads to reduced tumor growth in glioma models and improves the prognosis of tumor-bearing mice. This study underscores the critical role of CENPM in glioma and sheds light on potential therapeutic strategies.
{"title":"Upregulation of CENPM facilitates glioma progression via PI3K/AKT signaling pathway","authors":"Jiawei Chen , Fan Tang , Sichen Bao , Zhuqi Gao , Hong Chen , Qichuan Zhuge , Jianjing Yang , Ying Zhang","doi":"10.1016/j.ygeno.2025.111163","DOIUrl":"10.1016/j.ygeno.2025.111163","url":null,"abstract":"<div><div>Glioma, one of the most common types of primary brain tumors, presents considerable challenges due to its poor prognosis. Emerging research has demonstrated a strong connection between Centromere Protein M(CENPM) and tumor progression. However, the precise role of CENPM in glioma remains poorly understood. This study delves into the involvement of CENPM in glioma progression. Data analysis revealed that heightened CENPM expression correlates with worse patient outcomes and is highly expressed in glioma. In vitro experiments showed that reducing CENPM expression inhibits glioma cell proliferation and induces G0/G1 phase cell cycle arrest. Furthermore, RNA-seq and Western Blot analyses demonstrated that CENPM activates the PI3K/AKT signaling pathway in glioma cells. In vivo experiments confirmed that knocking down CENPM leads to reduced tumor growth in glioma models and improves the prognosis of tumor-bearing mice. This study underscores the critical role of CENPM in glioma and sheds light on potential therapeutic strategies.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111163"},"PeriodicalIF":3.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.ygeno.2025.111164
Jing Huang , Fei Qin , Jianling Li
Aldosterone-producing adenoma (APA) is a significant cause of primary aldosteronism, however, its cellular heterogeneity remains unclear. We performed single-cell RNA sequencing on adrenal tissues from three APA patients and three controls. We identified CAPS+ zona glomerulosa (ZG)-like cells in APA with upregulated lipogenesis, oxidative phosphorylation, and mTOR signaling, indicating metabolic reprogramming. Pseudotime analysis revealed disrupted differentiation and aberrant CYP11B1, CYP11B2, and SULT2A1 expression. Oncogenic Myc, Wnt, and G2/M pathways were activated in ZR-like clusters. APA showed immune infiltration (B cells, CD8+ T cells, M1 macrophages), angiogenic activation (VWF+ endothelial cells), and fibroblast-driven stromal remodeling via Hedgehog signaling. Our study provides a comprehensive single-cell atlas of APA, uncovering key tumorigenic mechanisms and identifying potential biomarkers (e.g., CAPS, VWF, UPK3B) and therapeutic targets, including mTOR and Hedgehog/Wnt pathways. These findings advance the genomic understanding of adrenal tumors and support precision medicine development.
{"title":"Single-cell transcriptomic analysis reveals metabolic reprogramming and tumor microenvironment remodeling in aldosterone-producing adenoma","authors":"Jing Huang , Fei Qin , Jianling Li","doi":"10.1016/j.ygeno.2025.111164","DOIUrl":"10.1016/j.ygeno.2025.111164","url":null,"abstract":"<div><div>Aldosterone-producing adenoma (APA) is a significant cause of primary aldosteronism, however, its cellular heterogeneity remains unclear. We performed single-cell RNA sequencing on adrenal tissues from three APA patients and three controls. We identified CAPS<sup>+</sup> zona glomerulosa (ZG)-like cells in APA with upregulated lipogenesis, oxidative phosphorylation, and mTOR signaling, indicating metabolic reprogramming. Pseudotime analysis revealed disrupted differentiation and aberrant <em>CYP11B1</em>, <em>CYP11B2</em>, and <em>SULT2A1</em> expression. Oncogenic Myc, Wnt, and G2/M pathways were activated in ZR-like clusters. APA showed immune infiltration (B cells, CD8<sup>+</sup> T cells, M1 macrophages), angiogenic activation (VWF<sup>+</sup> endothelial cells), and fibroblast-driven stromal remodeling via Hedgehog signaling. Our study provides a comprehensive single-cell atlas of APA, uncovering key tumorigenic mechanisms and identifying potential biomarkers (e.g., <em>CAPS</em>, <em>VWF</em>, <em>UPK3B</em>) and therapeutic targets, including mTOR and Hedgehog/Wnt pathways. These findings advance the genomic understanding of adrenal tumors and support precision medicine development.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111164"},"PeriodicalIF":3.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.ygeno.2025.111162
Fulei Wei , Xianzhi Zuo , Qiangdong Yang , Qianwen Li , Faxin Jin , Rui Ma , Guoliang Sun , Mingming Cui , Yuqiong Meng
Rainbow trout (Oncorhynchus mykiss) is one of the most widely farmed salmonid species globally. To investigate the mechanisms regulating muscle fat content and enhancing tolerance to high-lipid diets, transcriptomic changes in muscle tissues (myotomes and myosepta) were analyzed after treatment with an elevated dietary lipid level (30 %). The results revealed that myotomes and myosepta employed distinct strategies to maintain lipid homeostasis under elevated dietary lipids. Myotomes suppressed lipid deposition by upregulating lipoic acid synthesis to enhance lipolysis and reducing lipoprotein sialylation, while myosepta inhibited lipid storage through AMP metabolism modulation in adipocytes and the decreased function of phosphatidylinositol-4-phosphate (PI4P) binding. Beyond these tissue-specific strategies, both myotomes and myosepta also adopted some common approaches against lipid surplus. The downregulation of GFRAL4 balanced energy acquisition, and MBLH2-mediated lipolysis prevented ectopic deposition. Crucially, miRNAs coordinated tissue-specific and systemic adaptations to dietary lipid fluctuations mainly by targeting key genes involved in lipid metabolism pathways. Overall, these findings identified potential protein targets and regulatory pathways for regulating myoseptal fat content to improve meat flavor attributes, and elucidated the metabolic adaptation mechanisms of triploid rainbow trout to high-lipid diets.
{"title":"Divergent miRNA-mRNA networks contribute to tissue-specific lipid homeostasis in triploid rainbow trout skeletal muscle during high-lipid diet challenge","authors":"Fulei Wei , Xianzhi Zuo , Qiangdong Yang , Qianwen Li , Faxin Jin , Rui Ma , Guoliang Sun , Mingming Cui , Yuqiong Meng","doi":"10.1016/j.ygeno.2025.111162","DOIUrl":"10.1016/j.ygeno.2025.111162","url":null,"abstract":"<div><div>Rainbow trout (<em>Oncorhynchus mykiss</em>) is one of the most widely farmed salmonid species globally. To investigate the mechanisms regulating muscle fat content and enhancing tolerance to high-lipid diets, transcriptomic changes in muscle tissues (<em>myotomes</em> and <em>myosepta</em>) were analyzed after treatment with an elevated dietary lipid level (30 %). The results revealed that <em>myotomes</em> and <em>myosepta</em> employed distinct strategies to maintain lipid homeostasis under elevated dietary lipids. <em>Myotomes</em> suppressed lipid deposition by upregulating lipoic acid synthesis to enhance lipolysis and reducing lipoprotein sialylation, while <em>myosepta</em> inhibited lipid storage through AMP metabolism modulation in adipocytes and the decreased function of phosphatidylinositol-4-phosphate (PI4P) binding. Beyond these tissue-specific strategies, both <em>myotomes</em> and <em>myosepta</em> also adopted some common approaches against lipid surplus. The downregulation of <em>GFRAL4</em> balanced energy acquisition, and <em>MBLH2-</em>mediated lipolysis prevented ectopic deposition. Crucially, miRNAs coordinated tissue-specific and systemic adaptations to dietary lipid fluctuations mainly by targeting key genes involved in lipid metabolism pathways. Overall, these findings identified potential protein targets and regulatory pathways for regulating myoseptal fat content to improve meat flavor attributes, and elucidated the metabolic adaptation mechanisms of triploid rainbow trout to high-lipid diets.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111162"},"PeriodicalIF":3.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.ygeno.2025.111160
Endashaw Jebessa , Yanhua He , Hao Qu , Lin Chuxiao , Zhifeng Zhao , Haile Berihulay , Peng Chen , Xian Zou , Jian Ji , Dingming Shu , Chenglong Luo
Despite the integrative function of miRNAs and genes in chicken embryonic gonadal sex differentiation, their roles remain poorly understood. Here, we used RNA-seq to analyze 12 gonadal samples from embryonic days 5 (E5) and 9 (E9). Our analysis of miRNA and mRNA expression during this key developmental stage revealed five DEmiRNAs and 235 DEmRNAs consistently associated with left-right asymmetry in female gonads in both F5L vs F5R and F9L vs F9R comparisons. The interaction between DEmiRNAs and target DEmRNAs in the left-right asymmetry of embryonic gonadal development at E5 and E9 in chickens, along with the KEGG pathway enrichment analysis, revealed the involvement of several significant pathways. These include the complement and coagulation cascades, tight junctions, and synthesis and secretion of aldosterone. Differentially expressed miRNAs and target genes at embryonic days 5 and 9 reveal key molecular mechanisms driving gonadal sex differentiation in chickens.
{"title":"Transcriptome profile analysis of miRNA and mRNA in chicken embryo gonad sex differentiation","authors":"Endashaw Jebessa , Yanhua He , Hao Qu , Lin Chuxiao , Zhifeng Zhao , Haile Berihulay , Peng Chen , Xian Zou , Jian Ji , Dingming Shu , Chenglong Luo","doi":"10.1016/j.ygeno.2025.111160","DOIUrl":"10.1016/j.ygeno.2025.111160","url":null,"abstract":"<div><div>Despite the integrative function of miRNAs and genes in chicken embryonic gonadal sex differentiation, their roles remain poorly understood. Here, we used RNA-seq to analyze 12 gonadal samples from embryonic days 5 (E5) and 9 (E9). Our analysis of miRNA and mRNA expression during this key developmental stage revealed five DEmiRNAs and 235 DEmRNAs consistently associated with left-right asymmetry in female gonads in both F5L vs F5R and F9L vs F9R comparisons. The interaction between DEmiRNAs and target DEmRNAs in the left-right asymmetry of embryonic gonadal development at E5 and E9 in chickens, along with the KEGG pathway enrichment analysis, revealed the involvement of several significant pathways. These include the complement and coagulation cascades, tight junctions, and synthesis and secretion of aldosterone. Differentially expressed miRNAs and target genes at embryonic days 5 and 9 reveal key molecular mechanisms driving gonadal sex differentiation in chickens.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111160"},"PeriodicalIF":3.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1016/j.ygeno.2025.111158
Fanny Mollandin , Hervé Acloque , Maria Ballester , Marco Bink , Mario Calus , Daniel Crespo-Piazuelo , Pascal Croiseau , Sarah Djebali , Sylvain Foissac , Hélène Gilbert , Elisabetta Giuffra , Cervin Guyomar , Ole Madsen , Marie-José Mercat , Bruno da Costa Perez , Jani de Vos , Andrea Rau
Gene expression is a dynamic phenotype influenced by tissue-specific regulatory mechanisms, which can modulate expression directly or indirectly through cis or trans factors. Identifying genetic variants in these regulatory regions can improve both expression quantitative trait locus (eQTL) mapping and gene expression prediction. Whole genome sequences offer the possibility for enhanced eQTL mapping accuracy, but detecting causal variants remains challenging. Here, we evaluate the potential added-value of integrating tissue-specific epigenetic annotations, such as chromatin accessibility and methylation status, into within-breed genomic predictions of expression for three pig breeds. Functional annotations from early developmental stages improved eQTL mapping interpretability as shown by the enrichment of trait-relevant QTLs. However, despite the use of functional annotations, predictions across breeds remain challenging due to differences in genetic architectures. Our work contributes to the understanding of gene expression regulation in livestock and highlights the value of functional annotations, despite continued challenges for predictions across breeds.
{"title":"Guiding eQTL mapping and genomic prediction of gene expression in three pig breeds with tissue-specific epigenetic annotations from early development","authors":"Fanny Mollandin , Hervé Acloque , Maria Ballester , Marco Bink , Mario Calus , Daniel Crespo-Piazuelo , Pascal Croiseau , Sarah Djebali , Sylvain Foissac , Hélène Gilbert , Elisabetta Giuffra , Cervin Guyomar , Ole Madsen , Marie-José Mercat , Bruno da Costa Perez , Jani de Vos , Andrea Rau","doi":"10.1016/j.ygeno.2025.111158","DOIUrl":"10.1016/j.ygeno.2025.111158","url":null,"abstract":"<div><div>Gene expression is a dynamic phenotype influenced by tissue-specific regulatory mechanisms, which can modulate expression directly or indirectly through <em>cis</em> or <em>trans</em> factors. Identifying genetic variants in these regulatory regions can improve both expression quantitative trait locus (eQTL) mapping and gene expression prediction. Whole genome sequences offer the possibility for enhanced eQTL mapping accuracy, but detecting causal variants remains challenging. Here, we evaluate the potential added-value of integrating tissue-specific epigenetic annotations, such as chromatin accessibility and methylation status, into within-breed genomic predictions of expression for three pig breeds. Functional annotations from early developmental stages improved eQTL mapping interpretability as shown by the enrichment of trait-relevant QTLs. However, despite the use of functional annotations, predictions across breeds remain challenging due to differences in genetic architectures. Our work contributes to the understanding of gene expression regulation in livestock and highlights the value of functional annotations, despite continued challenges for predictions across breeds.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111158"},"PeriodicalIF":3.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.ygeno.2025.111154
Yan Wang , Jiahao Zhou , Mingqi Yang , Youhua Yao , Yongmei Cui , Xin Li , Baojun Ding , Xiaohua Yao , Kunlun Wu
Grain size critically determines both yield and quality in crops. This study systematically investigated two distinct qingke varieties with contrasting grain sizes through integrated dynamic phenotyping, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Key observations indicated that statistically significant differences in grain length and width between the two qingke varieties became apparent from 13 DAF. Transcriptome sequencing (RNA-seq) analysis revealed a peak in the number of differentially expressed genes (DEGs) at 13 days after flowering, indicating that gene expression patterns during this stage might regulate the establishment of grain length and width morphology. These DEGs were likely key regulators of grain dimensions. WGCNA analysis identified a highly correlated brown module enriched with MAPK pathway genes, which showed significant associations with grain size (length, width, thickness) and weight. Functional analysis of the MAPK pathway candidate gene HvPR1 demonstrated that its over-expression in barley significantly increased thousand-grain weight (TGW) while reducing grain hardness (GH), thereby uncovering a previously uncharacterized regulatory role in grain development. The observed reduction in grain hardness in over-expression lines was primarily attributed to decreased lignin and cellulose content. These results provide critical genetic resources and novel mechanistic insights to support precision breeding strategies for qingke and other cereal crops.
{"title":"HvPR1: A dual-role architect in balancing grain weight and hardness in barley","authors":"Yan Wang , Jiahao Zhou , Mingqi Yang , Youhua Yao , Yongmei Cui , Xin Li , Baojun Ding , Xiaohua Yao , Kunlun Wu","doi":"10.1016/j.ygeno.2025.111154","DOIUrl":"10.1016/j.ygeno.2025.111154","url":null,"abstract":"<div><div>Grain size critically determines both yield and quality in crops. This study systematically investigated two distinct qingke varieties with contrasting grain sizes through integrated dynamic phenotyping, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Key observations indicated that statistically significant differences in grain length and width between the two qingke varieties became apparent from 13 DAF. Transcriptome sequencing (RNA-seq) analysis revealed a peak in the number of differentially expressed genes (DEGs) at 13 days after flowering, indicating that gene expression patterns during this stage might regulate the establishment of grain length and width morphology. These DEGs were likely key regulators of grain dimensions. WGCNA analysis identified a highly correlated brown module enriched with MAPK pathway genes, which showed significant associations with grain size (length, width, thickness) and weight. Functional analysis of the MAPK pathway candidate gene <em>HvPR1</em> demonstrated that its over-expression in barley significantly increased thousand-grain weight (TGW) while reducing grain hardness (GH), thereby uncovering a previously uncharacterized regulatory role in grain development. The observed reduction in grain hardness in over-expression lines was primarily attributed to decreased lignin and cellulose content. These results provide critical genetic resources and novel mechanistic insights to support precision breeding strategies for qingke and other cereal crops.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 1","pages":"Article 111154"},"PeriodicalIF":3.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.ygeno.2025.111153
Miao Yang , Xiuming Mei , Xiaofeng Yu , Jing Wu , Yuwei Qiang , Xiaoxiao Wu , Hanxu Ji , Yufeng Li , Diyao Jiang , Jingjing Xu , Chi Zhang
Tilletia laevis is a fungal pathogen that causes the severe wheat disease known as common bunt, which is widespread in wheat-growing areas worldwide. Nevertheless, insufficient genome data hinders research at the molecular level. In this study, we reported a high-quality whole genome assembly of T. laevis isolated from China utilizing the integration of Illumina and PacBio sequencing technologies. The genome assembly consisted of 40 contigs with a total length of 38.09 Mb, a contig N50 of 1.50 Mb, and a maximum contig length of 2.61 Mb. The genome encoded 10,682 genes, with a notable enrichment of metabolism-related genes identified by functional annotations. The comparative genomic analysis was conducted between this assembly and closely related Tilletia strains, revealing its evolutionary trajectory. Overall, the genome assembly is currently the most continuous genome for T. laevis, facilitating future research on the pathogenic mechanism and control of this pathogen.
{"title":"Whole genome sequencing of Tilletia laevis, the fungal pathogen causing common bunt","authors":"Miao Yang , Xiuming Mei , Xiaofeng Yu , Jing Wu , Yuwei Qiang , Xiaoxiao Wu , Hanxu Ji , Yufeng Li , Diyao Jiang , Jingjing Xu , Chi Zhang","doi":"10.1016/j.ygeno.2025.111153","DOIUrl":"10.1016/j.ygeno.2025.111153","url":null,"abstract":"<div><div><em>Tilletia laevis</em> is a fungal pathogen that causes the severe wheat disease known as common bunt, which is widespread in wheat-growing areas worldwide. Nevertheless, insufficient genome data hinders research at the molecular level. In this study, we reported a high-quality whole genome assembly of <em>T. laevis</em> isolated from China utilizing the integration of Illumina and PacBio sequencing technologies. The genome assembly consisted of 40 contigs with a total length of 38.09 Mb, a contig N50 of 1.50 Mb, and a maximum contig length of 2.61 Mb. The genome encoded 10,682 genes, with a notable enrichment of metabolism-related genes identified by functional annotations. The comparative genomic analysis was conducted between this assembly and closely related <em>Tilletia</em> strains, revealing its evolutionary trajectory. Overall, the genome assembly is currently the most continuous genome for <em>T. laevis</em>, facilitating future research on the pathogenic mechanism and control of this pathogen.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111153"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idiopathic congenital nystagmus (ICN) is characterized by involuntary horizontal eye oscillations and is frequently associated with X-linked FRMD7 mutations. Despite over 150 FRMD7 variants have been reported, their pathogenic mechanisms remain poorly understood. In this study, we identified a novel FRMD7 deletion (c.742-211_1050+59del p.Leu249_Val351del) in an ICN-affected family. Minigenes analysis demonstrated that this FRMD7 mutation caused skipping of exon 9– 11. RT-qPCR and western blotting revealed unchanged FRMD7 mRNA levels but a significantly upregulated in protein expression. Structural modeling indicated the loss of a crucial amino acid segment in the mutated FRMD7 protein (FRMD7-m1). These findings suggest that this FRMD7 deletion disrupts protein translation and stability, contributing to ICN pathogenesis, and expand our understanding of FRMD7-related molecular mechanisms.
{"title":"Functional analysis of a novel segment deletion in the FRMD7 gene causing X-linked idiopathic congenital nystagmus","authors":"Xiaoli Zhao , Xinyang Li , Jian Yuan, Xiaolei Wang, Qinxue Meng, Xinwen Zhang","doi":"10.1016/j.ygeno.2025.111138","DOIUrl":"10.1016/j.ygeno.2025.111138","url":null,"abstract":"<div><div>Idiopathic congenital nystagmus (ICN) is characterized by involuntary horizontal eye oscillations and is frequently associated with X-linked <em>FRMD7</em> mutations. Despite over 150 <em>FRMD7</em> variants have been reported, their pathogenic mechanisms remain poorly understood. In this study, we identified a novel <em>FRMD7</em> deletion (c.742-211_1050+59del p.Leu249_Val351del) in an ICN-affected family. Minigenes analysis demonstrated that this <em>FRMD7</em> mutation caused skipping of exon 9– 11. RT-qPCR and western blotting revealed unchanged <em>FRMD7</em> mRNA levels but a significantly upregulated in protein expression. Structural modeling indicated the loss of a crucial amino acid segment in the mutated FRMD7 protein (<em>FRMD7</em>-m1). These findings suggest that this <em>FRMD7</em> deletion disrupts protein translation and stability, contributing to ICN pathogenesis, and expand our understanding of <em>FRMD7</em>-related molecular mechanisms.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111138"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.ygeno.2025.111156
Jun Xiang , Jingyi Cheng , Yidan Fan , Jiawen Wu , Zhaoyuan Lyu , Jiayu Gu , Jianjiang Xu , Ning Lyu
Purpose
Pterygium was a common progressive ocular disease with unclear pathogenesis. The aim of this study was to identify biomarkers associated with the integrated stress response (ISR) in pterygia and explore the underlying molecular mechanisms.
Methods
Differentially expressed genes (DEGs) were identified using transcriptome sequencing. ISR-related genes (IRGs) and DEGs were integrated to identify candidate genes, and biomarkers were identified by machine learning. A nomogram was generated using these biomarkers. Enrichment analysis, immune infiltration analysis, correlation analysis, construction of transcription-factor (TF)-mRNA-miRNA regulatory networks, drug prediction, and molecular docking were performed to assess the functional mechanisms underlying these biomarkers.
Results
EGLN3, HSPA8, and NDRG1 were identified as ISR-related biomarkers. EGLN3, HSPA8, and NDRG1 were associated with oxidative phosphorylation, cellular response to hypoxia, and decreased oxygen levels according to enrichment analysis. EGLN3 and NDRG1 were significantly and negatively correlated with immune cells, including immature B cells, but not HSPA8. ARNTL-EGLN3-hsa-miR-520a-3p, ARNTL-HSPA8-hsa-miR-520a-3p, and SNAPC4-NDRG1-hsa-miR-518a-5p played regulatory roles in pterygium development. Drug prediction and molecular docking analyses suggested Metribolone and Valproic Acid as potential therapeutic targets for pterygium. According to qRT-PCR, the expressions of EGLN3, HSPA8, and NDRG1 significantly differed between control and pterygium tissues.
Conclusions
EGLN3, HSPA8, and NDRG1 were identified as biomarkers associated with ISR in pterygium. The regulatory networks composed of differed expressions of ISR-related genes, miRNA-mRNA-TF regulatory axes, and immune response played crucial roles in the development of pterygium.
{"title":"Unveiling the role of integrated stress response in pterygium: EGLN3, HSPA8, and NDRG1 as novel biomarkers and therapeutic targets","authors":"Jun Xiang , Jingyi Cheng , Yidan Fan , Jiawen Wu , Zhaoyuan Lyu , Jiayu Gu , Jianjiang Xu , Ning Lyu","doi":"10.1016/j.ygeno.2025.111156","DOIUrl":"10.1016/j.ygeno.2025.111156","url":null,"abstract":"<div><h3>Purpose</h3><div>Pterygium was a common progressive ocular disease with unclear pathogenesis. The aim of this study was to identify biomarkers associated with the integrated stress response (ISR) in pterygia and explore the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) were identified using transcriptome sequencing. ISR-related genes (IRGs) and DEGs were integrated to identify candidate genes, and biomarkers were identified by machine learning. A nomogram was generated using these biomarkers. Enrichment analysis, immune infiltration analysis, correlation analysis, construction of transcription-factor (TF)-mRNA-miRNA regulatory networks, drug prediction, and molecular docking were performed to assess the functional mechanisms underlying these biomarkers.</div></div><div><h3>Results</h3><div><em>EGLN3</em>, <em>HSPA8</em>, and <em>NDRG1</em> were identified as ISR-related biomarkers. <em>EGLN3</em>, <em>HSPA8</em>, and <em>NDRG1</em> were associated with oxidative phosphorylation, cellular response to hypoxia, and decreased oxygen levels according to enrichment analysis. <em>EGLN3</em> and <em>NDRG1</em> were significantly and negatively correlated with immune cells, including immature B cells, but not <em>HSPA8</em>. ARNTL-EGLN3-hsa-miR-520a-3p, ARNTL-HSPA8-hsa-miR-520a-3p, and SNAPC4-NDRG1-hsa-miR-518a-5p played regulatory roles in pterygium development. Drug prediction and molecular docking analyses suggested Metribolone and Valproic Acid as potential therapeutic targets for pterygium. According to qRT-PCR, the expressions of <em>EGLN3</em>, <em>HSPA8</em>, and <em>NDRG1</em> significantly differed between control and pterygium tissues.</div></div><div><h3>Conclusions</h3><div><em>EGLN3, HSPA8,</em> and <em>NDRG1</em> were identified as biomarkers associated with ISR in pterygium. The regulatory networks composed of differed expressions of ISR-related genes, miRNA-mRNA-TF regulatory axes, and immune response played crucial roles in the development of pterygium.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111156"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.ygeno.2025.111136
Guangyi Chen , Junhui Zhang , Jiayi Wang , Wenxiu Chen , Haoran Li , Haoran Su , Shaoyi Dai , Yumei Tao , Yunxia Cao , Qiang Hong , Fenfen Xie
Liver lipid disorders are common in polycystic ovary syndrome (PCOS) patients. A DHEA-induced PCOS mouse model exhibited elevated liver triglyceride (TG) and total cholesterol (TC), reinforcing this association between liver lipids and PCOS. Liver transcriptomic sequencing revealed that 168 differentially expressed genes and 285 alternative splicing (AS) event genes, significantly enriching retinol metabolism. Further combined analyses showed the Cyp4a32 and Hsd17b6 genes were abnormally expressed in the livers of PCOS mice. AS analysis revealed that Cyp4a32 had upregulated exon skipping (SE), including SE and mutually exclusive exons (MXE), while among the modes of SE, MXE, and alternative 3′ splice site (A3SS), Hsd17b6 showed downregulated MXE. These findings suggest that Cyp4a32 and Hsd17b6 may change the retinol metabolism by modulating AS patterns, which then dysregulate hepatic lipid metabolism in PCOS. This study highlights potential therapeutic targets for PCOS-associated liver lipid disorders.
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