Human Gene最新文献_第6页

The LEPR gene: A multifaceted regulator of energy homeostasis, obesity pathogenesis, and metabolic health LEPR基因：能量稳态、肥胖发病机制和代谢健康的多方面调节因子

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-25 DOI: 10.1016/j.humgen.2025.201486

Isar Sharma , Nishutosh , Kritika Bakshi , Ritu Mahajan , Nisha Kapoor

Background & Aim

This review examines the leptin-LEPR axis and its role in regulating energy balance and obesity. The LEPR gene provides the essential instructions for synthesizing the leptin receptor, a protein of paramount importance within the neuroendocrine system that orchestrates energy balance. Leptin, an adipokine secreted primarily by adipose tissue, functions as a critical signal reflecting the body's energy stores. It modulates appetite and energy expenditure by binding to its cognate receptor, which is predominantly expressed in the hypothalamus.

Materials & methods

The authors comprehensively examined a wide range of studies to detail the function of the LEPR gene and the complex intracellular signalling pathways it initiates. The focus was on understanding how dysfunctions, from rare genetic mutations to common acquired leptin resistance, disrupt these homeostatic mechanisms.

Results

The review confirms that when leptin binds to its receptor, it initiates a complex cascade of intracellular signalling pathways. These include the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/Akt pathways. Dysfunction of the leptin-LEPR axis, whether stemming from rare genetic mutations leading to congenital leptin receptor deficiency or the more prevalent acquired leptin resistance observed in common obesity, severely disrupts these intricate homeostatic mechanisms. Such disruptions invariably manifest as profound hyperphagia (excessive hunger) and severe obesity.

Conclusion

A comprehensive understanding of the LEPR axis and its intricate signalling networks is therefore fundamental for elucidating the pathophysiology of obesity and for the development of effective therapeutic strategies.

背景与目的本文综述了瘦素- lepr轴及其在调节能量平衡和肥胖中的作用。LEPR基因为瘦素受体的合成提供了必要的指令，瘦素受体是神经内分泌系统中最重要的蛋白质，负责协调能量平衡。瘦素是一种主要由脂肪组织分泌的脂肪因子，是反映身体能量储存的关键信号。它通过结合其主要在下丘脑表达的同源受体来调节食欲和能量消耗。材料和方法作者全面检查了广泛的研究，详细介绍了LEPR基因的功能和它所启动的复杂的细胞内信号通路。研究的重点是了解从罕见的基因突变到常见的获得性瘦素抵抗等功能障碍是如何破坏这些体内平衡机制的。结果该综述证实，当瘦素与其受体结合时，它启动了一个复杂的细胞内信号通路级联。其中包括Janus kinase 2 (JAK2)/信号转导和转录激活因子3 （STAT3）和磷脂酰肌醇3激酶(PI3K)/Akt通路。无论是由于罕见的基因突变导致先天性瘦素受体缺乏，还是在常见肥胖中观察到的更普遍的获得性瘦素抵抗，瘦素- lepr轴的功能障碍都严重破坏了这些复杂的体内平衡机制。这种破坏总是表现为严重的贪食（过度饥饿）和严重的肥胖。因此，全面了解LEPR轴及其复杂的信号网络对于阐明肥胖的病理生理和制定有效的治疗策略至关重要。

{"title":"The LEPR gene: A multifaceted regulator of energy homeostasis, obesity pathogenesis, and metabolic health","authors":"Isar Sharma , Nishutosh , Kritika Bakshi , Ritu Mahajan , Nisha Kapoor","doi":"10.1016/j.humgen.2025.201486","DOIUrl":"10.1016/j.humgen.2025.201486","url":null,"abstract":"<div><h3>Background & Aim</h3><div>This review examines the leptin-LEPR axis and its role in regulating energy balance and obesity. The <em>LEPR</em> gene provides the essential instructions for synthesizing the leptin receptor, a protein of paramount importance within the neuroendocrine system that orchestrates energy balance. Leptin, an adipokine secreted primarily by adipose tissue, functions as a critical signal reflecting the body's energy stores. It modulates appetite and energy expenditure by binding to its cognate receptor, which is predominantly expressed in the hypothalamus.</div></div><div><h3>Materials & methods</h3><div>The authors comprehensively examined a wide range of studies to detail the function of the <em>LEPR</em> gene and the complex intracellular signalling pathways it initiates. The focus was on understanding how dysfunctions, from rare genetic mutations to common acquired leptin resistance, disrupt these homeostatic mechanisms.</div></div><div><h3>Results</h3><div>The review confirms that when leptin binds to its receptor, it initiates a complex cascade of intracellular signalling pathways. These include the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/Akt pathways. Dysfunction of the leptin-LEPR axis, whether stemming from rare genetic mutations leading to congenital leptin receptor deficiency or the more prevalent acquired leptin resistance observed in common obesity, severely disrupts these intricate homeostatic mechanisms. Such disruptions invariably manifest as profound hyperphagia (excessive hunger) and severe obesity.</div></div><div><h3>Conclusion</h3><div>A comprehensive understanding of the <em>LEPR</em> axis and its intricate signalling networks is therefore fundamental for elucidating the pathophysiology of obesity and for the development of effective therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201486"},"PeriodicalIF":0.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crosstalk between MitomiRs and cardiovascular disease mitomir与心血管疾病之间的串扰

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-25 DOI: 10.1016/j.humgen.2025.201488

Rashi Khare, Nilanjana Ghosh, Sunanda Arya, Swati Srivastava, Iti Garg

Background

Mitochondrial microRNAs (mitomiRs) have emerged as vital regulators in the etiology of cardiovascular disease (CVD). Differential mitomiR expression contributes to mitochondrial dysfunction which is a key contributor to heart failure, ischemia, and cardiomyopathic hypertrophy. Despite advances, the specific downstream pathways and molecular mechanisms influenced by mitomiRs remain inadequately defined. We have investigated mitomiRs which are associated with CVD.

Methods

A systematic literature review was conducted using PubMed to identify mitomiRs associated with cardiovascular disease. Experimentally validated target gene interactions were analyzed using MiRDB and MirTarBase. Protein-protein interaction (PPI) networks were constructed with STRING, and functional enrichment analyses, including Gene Ontology (GO) and KEGG pathway analyses, were performed using an SR plot. Hub gene identification was executed via the CytoHubba plugin in Cytoscape, pinpointing key regulatory nodes within the network.

Results

The present study identified 21 mitomiRs that modulate the coagulation gene pathway in cardiovascular disease. Notably, the amyloid precursor protein (APP) was recognized as a central hub. APP acts as a crucial intersection between the regulation of coagulation and mitochondrial protein clusters. Among the top 15 hub genes, APP was highlighted as a significant molecular regulator that potentially linked mitochondrial dysfunction with cardiovascular pathology.

Conclusion

Mitomir plays a critical role in the regulation of mitochondrial function in various cardiovascular diseases. Mitomir not only regulates the mitochondrial function but also are involved in the coagulation pathway. Mitochondrial dysfunction may have been a result of the involvement of amyloid precursor protein which itself is the main regulator of Alzheimer's disease. Hence uncovering the potential role behind APP in cardiovascular disease may help to unlock a potential target that is still missing in CVD.

线粒体microRNAs （mitomiRs）已成为心血管疾病（CVD）病因学中的重要调节因子。mitomiR的差异表达导致线粒体功能障碍，而线粒体功能障碍是心力衰竭、缺血和心肌病性肥厚的关键因素。尽管取得了进展，但受mitomir影响的特定下游途径和分子机制仍然不充分确定。我们研究了与心血管疾病相关的mitomir。方法利用PubMed进行系统文献综述，确定与心血管疾病相关的mitomir。实验验证的靶基因相互作用分析使用MiRDB和MirTarBase。使用STRING构建蛋白-蛋白相互作用（PPI）网络，并使用SR图进行功能富集分析，包括基因本体（GO）和KEGG通路分析。Hub基因鉴定是通过Cytoscape中的CytoHubba插件执行的，确定了网络中的关键调控节点。结果本研究鉴定了21个调节心血管疾病凝血基因通路的mitomir。值得注意的是，淀粉样前体蛋白（APP）被认为是一个中心枢纽。APP在凝血调节和线粒体蛋白簇之间起着至关重要的交叉作用。在前15个中心基因中，APP被强调为一个重要的分子调节因子，可能将线粒体功能障碍与心血管病理联系起来。结论mitomir在多种心血管疾病的线粒体功能调控中起重要作用。Mitomir不仅调节线粒体功能，还参与凝血途径。线粒体功能障碍可能是淀粉样蛋白前体蛋白参与的结果，淀粉样蛋白本身就是阿尔茨海默病的主要调节因子。因此，揭示APP在心血管疾病中的潜在作用可能有助于解开CVD中仍然缺失的潜在靶标。

{"title":"Crosstalk between MitomiRs and cardiovascular disease","authors":"Rashi Khare, Nilanjana Ghosh, Sunanda Arya, Swati Srivastava, Iti Garg","doi":"10.1016/j.humgen.2025.201488","DOIUrl":"10.1016/j.humgen.2025.201488","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial microRNAs (mitomiRs) have emerged as vital regulators in the etiology of cardiovascular disease (CVD). Differential mitomiR expression contributes to mitochondrial dysfunction which is a key contributor to heart failure, ischemia, and cardiomyopathic hypertrophy. Despite advances, the specific downstream pathways and molecular mechanisms influenced by mitomiRs remain inadequately defined. We have investigated mitomiRs which are associated with CVD.</div></div><div><h3>Methods</h3><div>A systematic literature review was conducted using PubMed to identify mitomiRs associated with cardiovascular disease. Experimentally validated target gene interactions were analyzed using MiRDB and MirTarBase. Protein-protein interaction (PPI) networks were constructed with STRING, and functional enrichment analyses, including Gene Ontology (GO) and KEGG pathway analyses, were performed using an SR plot. Hub gene identification was executed via the CytoHubba plugin in Cytoscape, pinpointing key regulatory nodes within the network.</div></div><div><h3>Results</h3><div>The present study identified 21 mitomiRs that modulate the coagulation gene pathway in cardiovascular disease. Notably, the amyloid precursor protein (APP) was recognized as a central hub. APP acts as a crucial intersection between the regulation of coagulation and mitochondrial protein clusters. Among the top 15 hub genes, APP was highlighted as a significant molecular regulator that potentially linked mitochondrial dysfunction with cardiovascular pathology.</div></div><div><h3>Conclusion</h3><div>Mitomir plays a critical role in the regulation of mitochondrial function in various cardiovascular diseases. Mitomir not only regulates the mitochondrial function but also are involved in the coagulation pathway. Mitochondrial dysfunction may have been a result of the involvement of amyloid precursor protein which itself is the main regulator of Alzheimer's disease. Hence uncovering the potential role behind APP in cardiovascular disease may help to unlock a potential target that is still missing in CVD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201488"},"PeriodicalIF":0.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of TBXA2R, TGF-β1 and Il-18 gene polymorphisms in the pathogenesis of pollen induced allergic asthma- a case-control study from West Bengal, India TBXA2R、TGF-β1和Il-18基因多态性在花粉诱导过敏性哮喘发病机制中的作用——来自印度西孟加拉邦的病例对照研究

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-23 DOI: 10.1016/j.humgen.2025.201485

Priti Mondal , Indranil Ganai , Himani Biswas , Saibal Moitra , Sanjoy Podder

Background

Allergic asthma is a chronic inflammatory disease of the respiratory system's conducting airways affecting 330 million people globally and causes intermittent attacks of breathlessness, wheezing, airway hyper-reactivity and coughing when exposed to specific allergens. Thromboxane A2 receptor (TBXA2R), Transforming Growth Factor Beta 1 (TGF-β1) and Interleukin-18 (IL-18) genes are reported to be involved in inflammatory and immune response pathways related to asthma. Based on the above facts it can be hypothesized that single nucleotide polymorphisms (SNPs) in these genes may be associated with the asthma phenotype.

Objectives

The present study aims to analyze the role of the TBXA2R rs4523, TGF-β1 rs1800470, IL-18 rs1946519, IL-18 rs1946518 and IL-18 rs549908 gene polymorphism in asthma susceptibility among the population of West Bengal, India.

Results

Maximum number of patients showed sensitivity towards Azadirachta indica (73.46 %), followed by Cocos nucifera (72.27 %), Caesalpinia pulcherrima (65.17 %), etc. Significant difference in genotype and allele frequencies was obtained between the study groups for TBXA2R rs4523 and IL-18 rs1946519 polymorphisms. Asthma patients possessed significantly higher frequency of TBXA2R rs4523 CC and IL-18 rs1946519 TT genotypes than controls. TBXA2R rs4523 CC and IL-18 rs1946519 TT genotype bearing patients showed highest intensity of SPT reactions. Patients bearing rs4523 CC and rs1946519 TT genotypes had significantly higher FEV1/FVC ratio, total IgE level and blood Eosinophil count than heterozygous or major genotype bearers.

Conclusion

The present study concluded that TBXA2R rs4523 and IL-18 rs1946519 polymorphisms are associated with allergic asthma susceptibility in the population of West Bengal, India.

过敏性哮喘是一种影响全球3.3亿人的呼吸系统传导气道的慢性炎症性疾病，当暴露于特定过敏原时，会导致间歇性呼吸困难、喘息、气道高反应性和咳嗽。据报道，血栓素A2受体（TBXA2R）、转化生长因子β1 （TGF-β1）和白细胞介素-18 （IL-18）基因参与哮喘相关的炎症和免疫反应途径。基于上述事实，可以假设这些基因的单核苷酸多态性（snp）可能与哮喘表型有关。目的分析TBXA2R rs4523、TGF-β1 rs1800470、IL-18 rs1946519、IL-18 rs1946518和IL-18 rss549908基因多态性在印度西孟加拉邦人群哮喘易感性中的作用。结果对印楝敏感的患者最多（73.46%），其次是椰子树（72.27%）、斑纹麻（65.17%）等。TBXA2R rs4523和IL-18 rs1946519多态性的基因型和等位基因频率在研究组之间存在显著差异。哮喘患者TBXA2R rs4523 CC和IL-18 rs1946519 TT基因型的频率明显高于对照组。携带TBXA2R rs4523 CC和IL-18 rs1946519 TT基因型的患者SPT反应强度最高。携带rs4523 CC和rs1946519 TT基因型的患者FEV1/FVC比值、总IgE水平和血嗜酸性粒细胞计数明显高于杂合子或主要基因型携带者。结论TBXA2R rs4523和IL-18 rs1946519多态性与印度西孟加拉邦人群变应性哮喘易感性相关。

{"title":"The role of TBXA2R, TGF-β1 and Il-18 gene polymorphisms in the pathogenesis of pollen induced allergic asthma- a case-control study from West Bengal, India","authors":"Priti Mondal , Indranil Ganai , Himani Biswas , Saibal Moitra , Sanjoy Podder","doi":"10.1016/j.humgen.2025.201485","DOIUrl":"10.1016/j.humgen.2025.201485","url":null,"abstract":"<div><h3>Background</h3><div>Allergic asthma is a chronic inflammatory disease of the respiratory system's conducting airways affecting 330 million people globally and causes intermittent attacks of breathlessness, wheezing, airway hyper-reactivity and coughing when exposed to specific allergens. Thromboxane A2 receptor (TBXA2R), Transforming Growth Factor Beta 1 (TGF-β1) and Interleukin-18 (IL-18) genes are reported to be involved in inflammatory and immune response pathways related to asthma. Based on the above facts it can be hypothesized that single nucleotide polymorphisms (SNPs) in these genes may be associated with the asthma phenotype.</div></div><div><h3>Objectives</h3><div>The present study aims to analyze the role of the TBXA2R rs4523, TGF-β1 rs1800470, IL-18 rs1946519, IL-18 rs1946518 and IL-18 rs549908 gene polymorphism in asthma susceptibility among the population of West Bengal, India.</div></div><div><h3>Results</h3><div>Maximum number of patients showed sensitivity towards <em>Azadirachta indica</em> (73.46 %), followed by <em>Cocos nucifera</em> (72.27 %), <em>Caesalpinia pulcherrima</em> (65.17 %), etc. Significant difference in genotype and allele frequencies was obtained between the study groups for TBXA2R rs4523 and IL-18 rs1946519 polymorphisms. Asthma patients possessed significantly higher frequency of TBXA2R rs4523 CC and IL-18 rs1946519 TT genotypes than controls. TBXA2R rs4523 CC and IL-18 rs1946519 TT genotype bearing patients showed highest intensity of SPT reactions. Patients bearing rs4523 CC and rs1946519 TT genotypes had significantly higher FEV1/FVC ratio, total IgE level and blood Eosinophil count than heterozygous or major genotype bearers.</div></div><div><h3>Conclusion</h3><div>The present study concluded that TBXA2R rs4523 and IL-18 rs1946519 polymorphisms are associated with allergic asthma susceptibility in the population of West Bengal, India.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201485"},"PeriodicalIF":0.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the risk of missense mutation rs137854486 (W1925R) of FN1 in papillary thyroid cancer: A computational and molecular dynamics approach 解读乳头状甲状腺癌中FN1错义突变rs137854486 （W1925R）的风险：计算和分子动力学方法

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-22 DOI: 10.1016/j.humgen.2025.201484

Febby Payva , Remya James , Amrisa Pavithra E. , Padmashree Das , Santhy K.S.

Papillary thyroid cancer (PTC) accounts for more than 85 % of all thyroid cancers. Three transcriptomic datasets of PTC, one each from humans (GSE138198), transgenic mice (GSE58689), and cell lines (GSE6339), were analysed for differentially expressed genes (DEGs). Seventy-three common DEGs were binned into significant pathways associated with cancer and immunity, for which gene ontology studies at the biological process, molecular function, and cellular component levels were performed. Protein–protein interaction (PPI) network construction and analysis of modules identified fibronectin 1 (FN1) as the critical hub gene in the pathophysiology of PTC. Survival analysis, immune infiltration analysis, and co-expression analysis of the hub genes were conducted to confirm their relationship with PTC prognosis. Analysis of four missense variants V692E, T817A, T817P and W1925R of FN1 associated with PTC, followed by structural analysis and molecular dynamics simulation, validated that the missense mutation rs137854486 (W1925R) of FN1 is significant in the tumorigenesis of PTC. FoldX predicted a significant positive ΔΔG (9.85646) value for W1925R, portraying substantial destabilization of FN1. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) values of the W1925R mutant indicate significant structural deviations in the protein, resulting in increased flexibility and reduced stability. Increased flexibility, particularly in regions critical for protein function, could affect the biological activity of the protein, with a crucial influence on the pathophysiology of PTC.

乳头状甲状腺癌（PTC）占所有甲状腺癌的85%以上。分别来自人（GSE138198）、转基因小鼠（GSE58689）和细胞系（GSE6339）的3个PTC转录组学数据集分析差异表达基因（DEGs）。73个常见的deg被归类为与癌症和免疫相关的重要途径，并在生物过程、分子功能和细胞成分水平上进行了基因本体论研究。蛋白-蛋白相互作用（Protein-protein interaction， PPI）网络构建及模块分析表明，纤连蛋白1 （fibronectin, FN1）是PTC病理生理中的关键枢纽基因。通过生存分析、免疫浸润分析和枢纽基因共表达分析，证实其与PTC预后的关系。对与PTC相关的FN1的4个错义变异V692E、T817A、T817P和W1925R进行分析，并进行结构分析和分子动力学模拟，验证了FN1的错义突变rs137854486 （W1925R）在PTC的肿瘤发生中具有重要意义。FoldX预测W1925R的显著阳性ΔΔG（9.85646）值，描绘了FN1的大量不稳定。W1925R突变体的均方根偏差（RMSD）、均方根波动（RMSF）和旋转半径（Rg）值表明，该蛋白存在明显的结构偏差，导致柔韧性增加，稳定性降低。灵活性的增加，特别是在蛋白质功能的关键区域，可能影响蛋白质的生物活性，对PTC的病理生理有重要影响。

{"title":"Deciphering the risk of missense mutation rs137854486 (W1925R) of FN1 in papillary thyroid cancer: A computational and molecular dynamics approach","authors":"Febby Payva , Remya James , Amrisa Pavithra E. , Padmashree Das , Santhy K.S.","doi":"10.1016/j.humgen.2025.201484","DOIUrl":"10.1016/j.humgen.2025.201484","url":null,"abstract":"<div><div>Papillary thyroid cancer (PTC) accounts for more than 85 % of all thyroid cancers. Three transcriptomic datasets of PTC, one each from humans (GSE138198), transgenic mice (GSE58689), and cell lines (GSE6339), were analysed for differentially expressed genes (DEGs). Seventy-three common DEGs were binned into significant pathways associated with cancer and immunity, for which gene ontology studies at the biological process, molecular function, and cellular component levels were performed. Protein–protein interaction (PPI) network construction and analysis of modules identified fibronectin 1 (FN1) as the critical hub gene in the pathophysiology of PTC. Survival analysis, immune infiltration analysis, and co-expression analysis of the hub genes were conducted to confirm their relationship with PTC prognosis. Analysis of four missense variants V692E, T817A, T817P and W1925R of FN1 associated with PTC, followed by structural analysis and molecular dynamics simulation, validated that the missense mutation rs137854486 (W1925R) of FN1 is significant in the tumorigenesis of PTC. FoldX predicted a significant positive ΔΔG (9.85646) value for W1925R, portraying substantial destabilization of FN1. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) values of the W1925R mutant indicate significant structural deviations in the protein, resulting in increased flexibility and reduced stability. Increased flexibility, particularly in regions critical for protein function, could affect the biological activity of the protein, with a crucial influence on the pathophysiology of PTC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201484"},"PeriodicalIF":0.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the frequency of Dectin-1 rs3901533 A > C and rs7309123 G > C gene variants in patients with acute myeloid leukemia (AML): A case-control study 急性髓性白血病（AML）患者Dectin-1 rs3901533 A > C和rs7309123 G > C基因变异频率的评估：一项病例对照研究

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-22 DOI: 10.1016/j.humgen.2025.201482

Davood Alinezhad Dezfuli , Ehsan Sarbazjoda , Nasrin Amirrajab , Tina Vosoughi , Alireza Momeni , Mohammad Ali Jalali Far

Background

Acute myeloid leukemia (AML) is a serious blood cancer mainly affecting adults, and its predisposing genetic factors remain unclear. While recent studies have linked dectin-1 polymorphisms to fungal infection risk in AML, their relationship with AML susceptibility has not been studied. This study evaluates the association between two dectin-1 single-nucleotide polymorphisms (SNPs) of rs3901533 A > C and rs7309123 G > C and AML risk.

Methods & materials

A total of 103 participants (53 AML patients and 50 age- and sex-matched healthy controls) from the Iranian population were included in this study. Both of the polymorphisms were genotyped using the tetra-ARMS-PCR method.

Results

The genotype distributions of rs3901533 A > C and rs7309123 G > C polymorphisms did not differ significantly between AML patients and controls under additive, dominant, or recessive genetic models (p-value > 0.05). Furthermore, allele frequencies for both SNPs showed no significant association with AML risk (p-value > 0.05). None of the genotypes or alleles increased the risk of AML (p-value > 0.05).

Conclusions

Neither the rs3901533 A > C nor the rs7309123 G > C polymorphisms are contributors to increased susceptibility to AML. However, further investigations are needed.

急性髓系白血病（acute myeloid leukemia， AML）是一种主要影响成人的严重血癌，其易感遗传因素尚不清楚。虽然最近的研究将dectin-1多态性与AML真菌感染风险联系起来，但它们与AML易感性的关系尚未研究。本研究评估了rs3901533 A >； C和rs7309123 G >； C的两个检测素-1单核苷酸多态性（snp）与AML风险之间的关系。方法材料本研究共纳入103名伊朗人群参与者（53名AML患者和50名年龄和性别匹配的健康对照）。两种多态性均采用4 - arms - pcr方法进行基因分型。结果rs3901533 A >； C和rs7309123 G >； C在加性、显性和隐性遗传模型下的基因型分布在AML患者和对照组之间无显著差异（p值>； 0.05）。此外，两种snp的等位基因频率与AML风险无显著关联（p值>； 0.05）。所有基因型或等位基因均未增加AML的风险（p值>； 0.05）。结论rs3901533 A >； C和rs7309123 G >； C多态性都不是AML易感性增加的因素。然而，还需要进一步的调查。

{"title":"Evaluation of the frequency of Dectin-1 rs3901533 A > C and rs7309123 G > C gene variants in patients with acute myeloid leukemia (AML): A case-control study","authors":"Davood Alinezhad Dezfuli , Ehsan Sarbazjoda , Nasrin Amirrajab , Tina Vosoughi , Alireza Momeni , Mohammad Ali Jalali Far","doi":"10.1016/j.humgen.2025.201482","DOIUrl":"10.1016/j.humgen.2025.201482","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) is a serious blood cancer mainly affecting adults, and its predisposing genetic factors remain unclear. While recent studies have linked dectin-1 polymorphisms to fungal infection risk in AML, their relationship with AML susceptibility has not been studied. This study evaluates the association between two dectin-1 single-nucleotide polymorphisms (SNPs) of rs3901533 A > C and rs7309123 G > C and AML risk.</div></div><div><h3>Methods & materials</h3><div>A total of 103 participants (53 AML patients and 50 age- and sex-matched healthy controls) from the Iranian population were included in this study. Both of the polymorphisms were genotyped using the tetra-ARMS-PCR method.</div></div><div><h3>Results</h3><div>The genotype distributions of rs3901533 A > C and rs7309123 G > C polymorphisms did not differ significantly between AML patients and controls under additive, dominant, or recessive genetic models (<em>p-value</em> > 0.05). Furthermore, allele frequencies for both SNPs showed no significant association with AML risk (<em>p-value</em> > 0.05). None of the genotypes or alleles increased the risk of AML (<em>p-value</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>Neither the rs3901533 A > C nor the rs7309123 G > C polymorphisms are contributors to increased susceptibility to AML. However, further investigations are needed.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201482"},"PeriodicalIF":0.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early-onset nephrolithiasis and persistent microscopic hematuria in a child with a novel pathogenic COL4A5 variant in Alport syndrome: A case report and literature review 早发性肾结石和持续性显微镜下血尿在儿童与新的致病性COL4A5变异在Alport综合征：1例报告和文献复习

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-19 DOI: 10.1016/j.humgen.2025.201483

Firoz Ahmad , Niladri Bose , Alec Correa , Sapna Sandal , Mukesh Kumar , Akashi Vyas , Amisha Shah , Meenu Angi , Jigar Suthar , Pooja Chaudhary , Anindyajit Banerjee , Spandan Chaudhary , Neeraj Arora

A 4-year-old male with persistent microscopic hematuria, hypocalciuria along with hypocitraturia. Renal ultrasound revealed bilateral microcalculi without structural anomalies. Ophthalmic and auditory evaluations were unremarkable. Family history indicated renal disease in the maternal aunt and maternal microscopic hematuria. Whole-exome sequencing (WES) identified a novel hemizygous nonsense variant in COL4A5 (NM_033380.3: c.1555C > T; p.Gln519*), truncating the protein at codon 519 of 1770. The variant, inherited from the mildly symptomatic mother (microscopic hematuria, right renal cyst), was absent in population databases and classified as pathogenic based on ACMG criteria (PVS1_Strong, PM2_Supporting, PP1_Supporting, PP4_Supporting). CytoScan 750 K array ruled out copy-number variations. This case expands the genotypic spectrum of Alport syndrome (AS), demonstrating an early presentation with nephrolithiasis, and underscores the diagnostic utility of WES in atypical inherited nephropathies.

1例4岁男性，镜下持续性血尿，低钙尿伴低尿。肾超声示双侧微结石，无结构异常。眼科和听觉评价无显著差异。家族史提示姨妈有肾脏疾病，母亲镜下血尿。全外显子组测序（WES）在COL4A5中发现了一个新的半合子无义变异（NM_033380.3: c.1555C >； T; p.Gln519*），截断了1770密码子519处的蛋白。该变异遗传自轻度症状的母亲（显微镜下血尿，右肾囊肿），在人群数据库中缺失，并根据ACMG标准（PVS1_Strong, pm2_support, pp1_support, pp4_support）分类为致病性。CytoScan 750 K阵列排除了拷贝数变化。本病例扩展了Alport综合征（AS）的基因型谱，显示了肾结石的早期表现，并强调了WES在非典型遗传性肾病中的诊断价值。

{"title":"Early-onset nephrolithiasis and persistent microscopic hematuria in a child with a novel pathogenic COL4A5 variant in Alport syndrome: A case report and literature review","authors":"Firoz Ahmad , Niladri Bose , Alec Correa , Sapna Sandal , Mukesh Kumar , Akashi Vyas , Amisha Shah , Meenu Angi , Jigar Suthar , Pooja Chaudhary , Anindyajit Banerjee , Spandan Chaudhary , Neeraj Arora","doi":"10.1016/j.humgen.2025.201483","DOIUrl":"10.1016/j.humgen.2025.201483","url":null,"abstract":"<div><div>A 4-year-old male with persistent microscopic hematuria, hypocalciuria along with hypocitraturia. Renal ultrasound revealed bilateral microcalculi without structural anomalies. Ophthalmic and auditory evaluations were unremarkable. Family history indicated renal disease in the maternal aunt and maternal microscopic hematuria. Whole-exome sequencing (WES) identified a novel hemizygous nonsense variant in <em>COL4A5</em> (NM_033380.3: c.1555C > T; p.Gln519*), truncating the protein at codon 519 of 1770. The variant, inherited from the mildly symptomatic mother (microscopic hematuria, right renal cyst), was absent in population databases and classified as pathogenic based on ACMG criteria (PVS1_Strong, PM2_Supporting, PP1_Supporting, PP4_Supporting). CytoScan 750 K array ruled out copy-number variations. This case expands the genotypic spectrum of Alport syndrome (AS), demonstrating an early presentation with nephrolithiasis, and underscores the diagnostic utility of WES in atypical inherited nephropathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201483"},"PeriodicalIF":0.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC LUSC和HNSCC中AREG基因的基因组、转录组学和表观基因组学改变

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-16 DOI: 10.1016/j.humgen.2025.201477

K. Akshaya Krishnan , P. Anitha , J. Vijayashree Priyadharsini , A. Paramasivam

Objectives

Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the AREG gene and their possible association with HNSCC and LUSC.

Methods

The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the AREG gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of AREG were assessed using the miRDB.

Results

The AREG gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of the AREG gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs hsa-miR-1185-1 and hsa-miR-487b were identified as potential targets of AREG, influencing the survival of patients with HNSCC.

Conclusions

The overexpression of AREG in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs hsa-miR-1185-1 and hsa-miR-487b, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.

目的头颈部癌症和肺部癌症具有相似的危险因素。这两种癌症患病率的增加强调了为其管理确定诊断、治疗和预后生物标志物的必要性。在此背景下，本研究旨在确定AREG基因的遗传改变及其与HNSCC和LUSC的可能关联。方法采用计算设计，利用以下数据库和工具来确定疾病表型与基因之间的关系。利用cBioPortal数据库分析了HNSCC和LUSC的TCGA数据集中AREG基因的遗传改变。使用UALCAN分析存活概率和基因表达谱。Welch’s检验显示正常组织与肿瘤组织之间有统计学意义。使用miRDB评估AREG的microRNA靶标。结果AREG基因在HNSCC中变异小于1%，在LUSC中变异小于4%。有趣的是，在HNSCC患者中观察到AREG基因的显著上调，而在LUSC中观察到下调。基因表达谱的升高与HNSCC患者预后不良相关，而低表达与LUSC患者预后良好相关。OSCC样品的实验验证显示，与正常样品相比，基因表达减少。此外，hsa-miR-1185-1和hsa-miR-487b被确定为AREG的潜在靶点，影响HNSCC患者的生存。结论AREG在HNSCC中的高表达，以及其不良预后，突出了该基因的致癌作用。有趣的是，表观遗传成分，特别是microrna hsa-miR-1185-1和hsa-miR-487b被发现下调，这表明它们对AREG表达有影响。这些发现需要通过功能研究进一步验证，以阐明AREG与癌症表型之间的关系。

{"title":"Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC","authors":"K. Akshaya Krishnan , P. Anitha , J. Vijayashree Priyadharsini , A. Paramasivam","doi":"10.1016/j.humgen.2025.201477","DOIUrl":"10.1016/j.humgen.2025.201477","url":null,"abstract":"<div><h3>Objectives</h3><div>Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the <em>AREG</em> gene and their possible association with HNSCC and LUSC.</div></div><div><h3>Methods</h3><div>The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the <em>AREG</em> gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of <em>AREG</em> were assessed using the miRDB.</div></div><div><h3>Results</h3><div>The <em>AREG</em> gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of <em>the AREG</em> gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em> were identified as potential targets of <em>AREG</em>, influencing the survival of patients with HNSCC.</div></div><div><h3>Conclusions</h3><div>The overexpression of <em>AREG</em> in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em>, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201477"},"PeriodicalIF":0.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel autosomal dominant variant in TMC1 and rare autosomal recessive variants in GJB2, SLC26A4 caused congenital hearing loss in Vietnamese children 一种新的TMC1常染色体显性变异和罕见的GJB2、SLC26A4常染色体隐性变异导致越南儿童先天性听力损失

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-14 DOI: 10.1016/j.humgen.2025.201480

Phuong Nhung Vu , Hai Ha Nguyen , Thi Huyen Thuong Ma , Thi Bich Ngoc Tran , Thi Kim Phuong Doan , Thi Lan Anh Luong , Tien Truong Dang , Dang Ton Nguyen

Background

Hearing loss in children can lead to consequences such as failure in speech, language, education and poor quality of life. This study investigated five Vietnamese families, one with all three children and others with one child suffered from congenital hearing loss to identify genetic cause of the disease.

Methods and results

Whole exome sequencing was performed for one proband of each family. Subsequently, Sanger sequencing was used for validation the genetic variants in the patients as well as other family members including parents and siblings. A novel variant in TMC1 (c.2209C > T) was detected in the affected child of family 1, which arose as a de novo mutation. In all three affected children of family 2, compound heterozygous variants were detected in SLC26A4 (c.754 T > C, c.1229C > T). In the affected children of family 4 and 5, compound heterozygous of GJB2 (c.109G > A, c.428G > A) and a homozygous deletion in GJB2 (c.235delC) were detected, respectively. In family 3, two genetic variants identified in deafness causing genes MYO7A (c.4795C > T) and MYO15A (c.7547C > T) of the patient in heterozygous state. Sangger sequencing identified only one pathogenic variant in each parent of family 2, 4 and 5. Similarly, existence of double heterozygote in MYO7A/MYO15A was not identified in the parents and remaining unaffected child in family 3.

Conclusions

This study contributed to expand genetic variants spectrum in Vietnamese hearing loss pediatrics. Identifying the genetic causes is crucial for early management of hearing loss patients and giving genetic counseling for further pregnancies of high-risk couples.

儿童听力损失可导致诸如言语、语言、教育和生活质量低下等后果。本研究调查了五个越南家庭，其中一个家庭有三个孩子，另一个家庭有一个孩子患有先天性听力损失，以确定该疾病的遗传原因。方法与结果对每个家族1个先证者进行全外显子组测序。随后，Sanger测序用于验证患者以及其他家庭成员（包括父母和兄弟姐妹）的遗传变异。在家族1的患病儿童中检测到一种新的TMC1变异（c.2209C >； T），这是一种新生突变。在家族2的所有3例患儿中，均检测到SLC26A4的复合杂合变异体（c.754）T >； C, C .1229C >； T)。家族4和家族5患儿分别检测到GJB2复合杂合基因（c.109G >； A, c.428G >； A）和GJB2纯合基因缺失（c.235delC）。在家族3中，在杂合状态患者的致聋基因MYO7A （c.4795C >； T）和MYO15A （c.7547C >； T）中鉴定出两个遗传变异。桑格测序仅在家族2、4和5的每个亲本中发现一个致病变异。同样，在父母和家庭3中未发现MYO7A/MYO15A双杂合子的存在。结论本研究有助于扩大越南听力损失儿科的遗传变异谱。确定遗传原因对于听力损失患者的早期管理和为高危夫妇的进一步怀孕提供遗传咨询至关重要。

{"title":"A novel autosomal dominant variant in TMC1 and rare autosomal recessive variants in GJB2, SLC26A4 caused congenital hearing loss in Vietnamese children","authors":"Phuong Nhung Vu , Hai Ha Nguyen , Thi Huyen Thuong Ma , Thi Bich Ngoc Tran , Thi Kim Phuong Doan , Thi Lan Anh Luong , Tien Truong Dang , Dang Ton Nguyen","doi":"10.1016/j.humgen.2025.201480","DOIUrl":"10.1016/j.humgen.2025.201480","url":null,"abstract":"<div><h3>Background</h3><div>Hearing loss in children can lead to consequences such as failure in speech, language, education and poor quality of life. This study investigated five Vietnamese families, one with all three children and others with one child suffered from congenital hearing loss to identify genetic cause of the disease.</div></div><div><h3>Methods and results</h3><div>Whole exome sequencing was performed for one proband of each family. Subsequently, Sanger sequencing was used for validation the genetic variants in the patients as well as other family members including parents and siblings. A novel variant in <em>TMC1</em> (c.2209C > T) was detected in the affected child of family 1, which arose as a <em>de novo</em> mutation. In all three affected children of family 2, compound heterozygous variants were detected in <em>SLC26A4</em> (c.754 T > C, c.1229C > T). In the affected children of family 4 and 5, compound heterozygous of <em>GJB2</em> (c.109G > A, c.428G > A) and a homozygous deletion in <em>GJB2</em> (c.235delC) were detected, respectively<em>.</em> In family 3, two genetic variants identified in deafness causing genes <em>MYO7A</em> (c.4795C > T) and <em>MYO15A</em> (c.7547C > T) of the patient in heterozygous state. Sangger sequencing identified only one pathogenic variant in each parent of family 2, 4 and 5. Similarly, existence of double heterozygote in <em>MYO7A</em>/<em>MYO15A</em> was not identified in the parents and remaining unaffected child in family 3.</div></div><div><h3>Conclusions</h3><div>This study contributed to expand genetic variants spectrum in Vietnamese hearing loss pediatrics. Identifying the genetic causes is crucial for early management of hearing loss patients and giving genetic counseling for further pregnancies of high-risk couples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201480"},"PeriodicalIF":0.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knockdown of histone H1–5 gene affects the sensitivity of MRC-5 and HeLa cells to DNA damaging agents 组蛋白H1-5基因敲低影响MRC-5和HeLa细胞对DNA损伤剂的敏感性

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201475

Tigran Harutyunyan , Anzhela Sargsyan , Gohar Tadevosyan , Lily Kalashyan , Rouben Aroutiounian , Galina Hovhannisyan

Linker histone H1.5, encoded by the H1–5 gene, plays a key role in chromatin compaction and genome stability. However, its role in cellular responses to mutagens is still poorly understood. Here, we analyzed the genotoxic effects of the standard genotoxic drugs doxorubicin (DOX) and mitomycin C (MMC) at non-cytotoxic concentrations after 24 h of treatment in normal lung fibroblasts (MRC-5) and cervical carcinoma cells (HeLa) with H1–5 gene knockdown (KD). Using CRISPR-Cas9, we achieved significant repression of H1–5 expression. Alkaline DNA comet assay and cytokinesis-block micronucleus assay showed that H1–5 KD significantly increased spontaneous and mutagen-induced DNA and chromosome damage levels in both cell lines (p < 0.05). Our results suggest that H1–5 gene deficiency makes DNA more susceptible to genotoxic impact while its mechanistic role in occurrence of DNA and chromosome damage requires further elucidation.

由H1-5基因编码的连接蛋白H1.5在染色质压实和基因组稳定性中起关键作用。然而，它在细胞对诱变剂反应中的作用仍然知之甚少。在这里，我们分析了标准基因毒性药物多柔比星（DOX）和丝裂霉素C （MMC）在治疗24小时后的非细胞毒性浓度对正常肺成纤维细胞（MRC-5）和H1-5基因敲低（KD）的宫颈癌细胞（HeLa）的遗传毒性作用。使用CRISPR-Cas9，我们实现了H1-5表达的显著抑制。碱性DNA彗星试验和细胞分裂阻滞微核试验显示，H1-5 KD显著增加了两种细胞系的自发和诱变诱导的DNA和染色体损伤水平（p < 0.05）。我们的研究结果表明，H1-5基因缺失使DNA更容易受到遗传毒性的影响，但其在DNA和染色体损伤发生中的机制有待进一步阐明。

引用次数: 0

Single-cell transcriptomics exposes an uncharacterized lncRNA governing colorectal cancer metastasis 单细胞转录组学揭示了一种未表征的lncRNA控制结直肠癌转移

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201479

Abbas Heydari Lori , Nahid Askari , Hossein Pourghadamyari

Colorectal cancer (CRC) exhibits significant molecular heterogeneity, with long non-coding RNAs (lncRNAs) playing crucial regulatory roles. This study identifies LncRNA01996 as a key oncogenic driver upregulated in CRC tumors compared to adjacent normal tissues, with expression levels correlating directly with advancing cancer stage (Stage I to IV). Mechanistically, LncRNA01996 stabilizes β-catenin, hyperactivating the Wnt signaling pathway while simultaneously suppressing E-CADHERIN expression a critical factor in maintaining cellular adhesion. This dual action promotes cancer cell invasion and metastasis. Additionally, LncRNA01996 transcriptionally activates MYC, amplifying its oncogenic effects.

Clinically, high LncRNA01996 expression is linked to aggressive tumor features, elevated serum markers (CEA, CA19–9), and shorter overall survival in patients. These findings were consistent across patient tissues, cell lines (SW480, SKM), and single-cell RNA sequencing data, confirming its role in diverse CRC microenvironments.

In summary, LncRNA01996 drives CRC progression by dysregulating Wnt/β-catenin signaling, disrupting cell adhesion, and amplifying MYC-driven malignancy. Its strong association with advanced disease and poor outcomes positions LncRNA01996 as a promising prognostic biomarker and a compelling therapeutic target for intercepting CRC metastasis.

结直肠癌（CRC）表现出明显的分子异质性，其中长链非编码rna （lncRNAs）发挥着至关重要的调控作用。本研究确定LncRNA01996是CRC肿瘤中与邻近正常组织相比上调的关键致癌驱动因子，其表达水平与癌症进展（I期至IV期）直接相关。从机制上讲，LncRNA01996稳定β-catenin，过度激活Wnt信号通路，同时抑制E-CADHERIN的表达，这是维持细胞粘附的关键因素。这种双重作用促进了癌细胞的侵袭和转移。此外，LncRNA01996转录激活MYC，放大其致癌作用。在临床上，LncRNA01996的高表达与侵袭性肿瘤特征、血清标志物（CEA、CA19-9）升高和患者总生存期缩短有关。这些发现在患者组织、细胞系（SW480、SKM）和单细胞RNA测序数据中是一致的，证实了其在不同CRC微环境中的作用。总之，LncRNA01996通过失调Wnt/β-catenin信号、破坏细胞粘附和放大myc驱动的恶性肿瘤来驱动结直肠癌的进展。LncRNA01996与晚期疾病和不良预后的强烈关联使其成为一种有前景的预后生物标志物和阻断结直肠癌转移的令人信服的治疗靶点。

{"title":"Single-cell transcriptomics exposes an uncharacterized lncRNA governing colorectal cancer metastasis","authors":"Abbas Heydari Lori , Nahid Askari , Hossein Pourghadamyari","doi":"10.1016/j.humgen.2025.201479","DOIUrl":"10.1016/j.humgen.2025.201479","url":null,"abstract":"<div><div>Colorectal cancer (CRC) exhibits significant molecular heterogeneity, with long non-coding RNAs (lncRNAs) playing crucial regulatory roles. This study identifies <em>LncRNA01996</em> as a key oncogenic driver upregulated in CRC tumors compared to adjacent normal tissues, with expression levels correlating directly with advancing cancer stage (Stage I to IV). Mechanistically, <em>LncRNA01996</em> stabilizes β-catenin, hyperactivating the Wnt signaling pathway while simultaneously suppressing <em>E-CADHERIN</em> expression a critical factor in maintaining cellular adhesion. This dual action promotes cancer cell invasion and metastasis. Additionally, <em>LncRNA01996</em> transcriptionally activates MYC, amplifying its oncogenic effects.</div><div>Clinically, high <em>LncRNA01996</em> expression is linked to aggressive tumor features, elevated serum markers (CEA, CA19–9), and shorter overall survival in patients. These findings were consistent across patient tissues, cell lines (SW480, SKM), and single-cell RNA sequencing data, confirming its role in diverse CRC microenvironments.</div><div>In summary, <em>LncRNA01996</em> drives CRC progression by dysregulating Wnt/β-catenin signaling, disrupting cell adhesion, and amplifying <em>MYC</em>-driven malignancy. Its strong association with advanced disease and poor outcomes positions <em>LncRNA01996</em> as a promising prognostic biomarker and a compelling therapeutic target for intercepting CRC metastasis.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201479"},"PeriodicalIF":0.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0