Human Gene最新文献

{"title":"Identification of a rare synonymous beta globin variant, HBB: c.60C>T in an Afghan Family as a benign variant","authors":"Zahra Taherian-Esfahani,&nbsp;Hamideh Namazi","doi":"10.1016/j.humgen.2025.201481","DOIUrl":"10.1016/j.humgen.2025.201481","url":null,"abstract":"<div><div>Beta thalassemia is a common autosomal recessive disorder. In this study, we report a rare beta globin gene variant, <em>HBB</em>: c.60C&gt;T, identified in an Afghan Family.</div><div>Sequencing of a 30 year old pregnant woman and her children showed that this synonymous variant, when present alongside other pathogenic HBB mutations, does not affect beta globin production. In the proband, hematological findings were not consistent with a beta thalassemia minor phenotype. Although this variant has been reported in Clinvar as a variant of uncertain significance (VUS), our findings support its classification as likely benign.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201481"},"PeriodicalIF":0.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219144","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}

{"title":"Clinical, genetic, and bioinformatics analysis of a novel TANGO2 mutation (c.263G > A) in an Iranian Azeri Turkish child with lethal metabolic encephalopathy","authors":"Elnaz Akbari ,&nbsp;Asal Asghari Sarfaraz ,&nbsp;Mortaza Bonyadi ,&nbsp;Mohammad Barzegar","doi":"10.1016/j.humgen.2025.201478","DOIUrl":"10.1016/j.humgen.2025.201478","url":null,"abstract":"<div><div>TANGO2-related disorder exhibits significant genotypic and phenotypic heterogeneity, and the clinical significance of novel variants often requires confirmation through detailed case reporting. This case report describes a female child born to consanguineous parents with an unremarkable prenatal and perinatal history. Initial development was normal, but by the second year of life, she exhibited developmental regression, and seizures, which were controlled with levetiracetam. At age 5, she presented with acute encephalopathy, dark urine, rhabdomyolysis, hypoglycemia, and hyperammonemia following a febrile illness. Whole-exome sequencing (WES) identified a novel homozygous <em>TANGO2</em> variant (c.263G &gt; A, p.Arg88Gln), confirmed via Sanger sequencing, with both parents being heterozygous carriers. Bioinformatics analysis predicted pathogenic effects, including potential exon skipping and protein structural alterations. The variant was absent in 430 ethnically matched controls and major population databases (gnomAD, 1000 Genomes), supporting its pathogenicity. Despite management, the patient experienced recurrent metabolic crises and ultimately succumbed to severe rhabdomyolysis and renal failure at age 8. This case underscores the severe phenotypic consequences of biallelic <em>TANGO2</em> mutations, including developmental delay, metabolic instability, and early mortality, while highlighting the importance of genetic diagnosis in unexplained pediatric encephalopathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201478"},"PeriodicalIF":0.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057241","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}

{"title":"Glioma in different life stages: A comparative analysis of adult and pediatric tumors","authors":"Ajia Ashraf ,&nbsp;Armeen Ashraf ,&nbsp;Lubna Khan ,&nbsp;Shahrukh Shaikh ,&nbsp;Farina Hanif","doi":"10.1016/j.humgen.2025.201476","DOIUrl":"10.1016/j.humgen.2025.201476","url":null,"abstract":"<div><div>Gliomas are one of the most common primary brain tumors and their prognosis is highly dependent on patient-specific factors. The objective of our review is to detail how age influences the epidemiology, molecular pathogenesis, prognosis, and treatment of gliomas. A literature search was conducted for adult and pediatric gliomas (PG) at Google Scholar and PubMed, with relevant keywords like gliomas, World Health Organization (WHO) classification, histology, and treatment, etc., and papers published until 2023 were reviewed. It was found that males and non-Hispanic white people are particularly at risk in both age categories. People with poor socioeconomic status are more likely to have PG. While the overall incidence of adult gliomas has been declining, glioblastoma (GBM) occurrence has been rising. The latest WHO classification of central nervous system (CNS) tumors has highlighted the molecular aberrations to further stratify adult and PG, and literature review revealed how each type has unique histological features. The first line treatment for both groups is surgery followed by adjuvant radio- and chemotherapy, although radiotherapy use for children remains controversial. PGs can also be treated with targeted therapy of the Mitogen-activated protein kinase (MAPK) pathway and currently, anti-cancer drugs are being investigated. By juxtaposing pediatric and adult gliomas, several theories can be proposed about how certain gliomas develop at specific ages, how they vary in their presentations and management, and what can be further explored to improve patient outcomes. This information is pivotal for understanding not only how age influences the development of certain mutations but also how treatment varies according to a patient's age.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201476"},"PeriodicalIF":0.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044158","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}

{"title":"Effectiveness of sesamol in alleviating neuroinflammation associated with Parkinson's disease","authors":"Rohini Durairaj ,&nbsp;Manjunathan Jagadeesan ,&nbsp;S. Shireen Farhana ,&nbsp;Shobana Chandrasekar ,&nbsp;Usharani Boopathy ,&nbsp;Parthiban Brindha Devi ,&nbsp;Pasiyappazham Ramasamy","doi":"10.1016/j.humgen.2025.201474","DOIUrl":"10.1016/j.humgen.2025.201474","url":null,"abstract":"<div><h3>Objectives</h3><div>A chronic progressive neurodegenerative disorder, Parkinson's disease (PD) is associated with motor impairment with elderly people. The cytokines and chemokines network are very complex and participate to balance the proinflammatory processes, apoptosis and cell existence. So, it is necessary to unravel the inflammatory process in PD. Increased nuclear factor kappa B, expression of cytokines, increased activation of microglia participate in the inflammatory process of PD. The activation of glial fibrillary acidic protein (GFAP) gene and protein results in the activation of astroglial cells which ends up with neurodegeneration and central nervous damage. Natural compounds carry a huge amount of antioxidant properties with health benefits and phenolic compounds is a natural dietary source.</div></div><div><h3>Methods</h3><div>Quantitative determination of serum CRP, immunohistochemical study was carried out along with the molecular studies such as (RT-PCR) and western blotting.</div></div><div><h3>Results</h3><div>Sesamol treatment decreased the C- Reactive protein level in serum of experimental animals. Sesamol also increased the tyrosine hydroxylase cells in rotenone-induced animals. The gene and protein expressions of NF-κB (p65), Tumor necrosis factor-α, cyclo oxygeanse-2, inducible nitric oxide synthase, interleukin-1β and GFAP were also reduced in SES treated animals.</div></div><div><h3>Conclusion</h3><div>Sesamol served as an anti-inflammatory compound in ROT-induced animal model of PD. This work mainly concentrates on the molecular mechanism of phenolic compound sesamol on rotenone induced PD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201474"},"PeriodicalIF":0.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019246","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}

{"title":"The role of a novel m6A reader CSTF2 amplification and overexpression in head and neck cancer development","authors":"Paramasivam Arumugam ,&nbsp;Chandra Pandi ,&nbsp;Vijayashree Priyadharsini Jayaseelan","doi":"10.1016/j.humgen.2025.201473","DOIUrl":"10.1016/j.humgen.2025.201473","url":null,"abstract":"<div><h3>Objective</h3><div>This study examines the oncogenic role of cleavage stimulation factor subunit 2 (CSTF2), a newly identified N6-methyladenosine (m6A)-binding protein in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). We also explored its amplification-driven overexpression, its prognostic significance, and its mechanistic contributions to tumor aggressiveness.</div></div><div><h3>Method</h3><div>A dataset of patients with HNSCC was used from the Cancer Genome Atlas (TCGA), which included information on clinical characteristics. Moreover, mRNA and protein expression data of CSTF2 were obtained from the Human Protein Atlas (HPA) database. Additionally, <em>CSTF2</em> mRNA levels were validated in an independent cohort of HNSCC patient tissues and cell lines using real-time PCR. The prognostic significance of <em>CSTF2</em> was evaluated using Kaplan-Meier survival plots. Additionally, protein-protein interaction networks of CSTF2 were established using the GeneMANIA database, and functional enrichment analysis was performed with Metascape.</div></div><div><h3>Result</h3><div>The study demonstrated that the <em>CSTF2</em> gene was significantly amplified, which correlated with elevated mRNA expression. Moreover, independent cohort analysis confirmed that <em>CSTF2</em> was overexpressed in HNSCC tissues and cell lines compared to non-tumorous tissues and normal cells. In addition, protein levels were markedly higher in HNSCC tissues, and elevated <em>CSTF2</em> mRNA expression was associated with poorer overall survival. Functional enrichment analysis showed that CSTF2 is involved in regulating oncogenic processes and the progression of HNSCC.</div></div><div><h3>Conclusion</h3><div>These data indicate that the <em>CSTF2</em> gene is amplified and overexpressed in HNSCC, indicating that this gene could be a significant prognostic marker and a potential therapeutic target for HNSCC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201473"},"PeriodicalIF":0.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044157","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}

{"title":"Genetic convergence and diversity: A comparative analysis of Egyptian autosomal STR profiles within global populations","authors":"Sagy Elzalabany ,&nbsp;Ibrahim H. Aboughaleb ,&nbsp;Mohamed Hisham Fouad Aref ,&nbsp;Tarek Taha ,&nbsp;Khaled Amer ,&nbsp;Sahar Fawzi ,&nbsp;Olfat Shaker","doi":"10.1016/j.humgen.2025.201472","DOIUrl":"10.1016/j.humgen.2025.201472","url":null,"abstract":"<div><h3>Background and objective</h3><div>Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.</div></div><div><h3>Methods</h3><div>Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.</div></div><div><h3>Results</h3><div>The Egyptian STR profile showed moderate to high correlation (<em>r</em> &gt; 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.</div></div><div><h3>Conclusions</h3><div>Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201472"},"PeriodicalIF":0.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044052","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}

{"title":"Assessment of the PCR inhibitory effect of the hair dye constituents and its role in forensic DNA analysis","authors":"Hirak Ranjan Dash ,&nbsp;Vaishnavi Gupta ,&nbsp;Dnyaneshwar Tanpure ,&nbsp;Braja Kishore Mohapatra","doi":"10.1016/j.humgen.2025.201471","DOIUrl":"10.1016/j.humgen.2025.201471","url":null,"abstract":"<div><div>Hair is among the most frequent types of biological evidence recovered at crime scenes, playing a crucial role in identifying culprits. Often, the recovered hair samples are dyed with various routinely used hair dyes. A survey of 182 individuals showed that the majority (82 %) of individuals dye their hair frequently, at least once a month. Cetearyl alcohol, propylene glycol, and disodium EDTA are the most common ingredients of the commercially available hair dyes. <em>In-silico</em> analysis predicted that the citric acid component of hair dye has the strongest affinity with Taq Polymerase (−6.1 Kcal/mol), followed by ascorbic acid (−5.5 Kcal/mol), resorcinol (−5.0 Kcal/mol), trisodium EDTA (−4.8 Kcal/mol), phosphoric acid (−4.0 Kcal/mol), glycerin and cetyl alcohol (−3.7 Kcal/mol), propylene glycol (−3.5 Kcal/mol), ethanolamine (−3.0 Kcal/mol) and hydrogen peroxide (−2.9 Kcal/mol). Molecular docking studies further revealed that the residues of arginine, threonine, glutamine, lysine, threonine, asparagine, serine, aspartic acid, phenylalanine, leucine, methionine, and tryptophan are the responsible motifs of Taq Polymerase which bind with different hair dye chemical constituents. In a singleplex PCR, the <em>CYCLO</em> gene was amplified only in the presence of cetyl alcohol, glycerin, and ethanolamine. All 23 STR markers were amplified using the Fusion 6C kit in the presence of hair dyes. However, the dye constituents adversely affected the Locus Balance of the STR profiles. Thus, most of the hair dye components act as potential PCR inhibitors by interacting with Taq Polymerase and suitable mitigation strategies should be employed for such forensic biological samples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201471"},"PeriodicalIF":0.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917761","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}

{"title":"Altered expression patterns of lncRNA MEG3 and LINC01611 in patients with colorectal cancer","authors":"Niloofar Faraji ,&nbsp;Mohammad Almasi ,&nbsp;Majid Mirmazloumi ,&nbsp;Nasim Padasht ,&nbsp;Sahand Sadat Mansouri ,&nbsp;Fatemeh Ghaderibarmi ,&nbsp;Haniyeh Royatpour ,&nbsp;Fatemeh Modaresi ,&nbsp;Kourosh Kazempour Samak ,&nbsp;Fahimeh Abedini Bajgiran ,&nbsp;Tahereh Zeinali ,&nbsp;Narges Eslami ,&nbsp;Dariush Shanehbandi ,&nbsp;Ali Salehzadeh","doi":"10.1016/j.humgen.2025.201470","DOIUrl":"10.1016/j.humgen.2025.201470","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at <em>P</em> &lt; 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (<em>n</em> = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, <em>P</em> = 0.038) and LINC01611 (1.03-fold, <em>P</em> = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (<em>P</em> &lt; 0.05), while other variables showed no statistically significant association (<em>P</em> &gt; 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (<em>r</em> = 0.649, <em>P</em> &lt; 0.001) and margin (<em>r</em> = 0.424, <em>P</em> = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201470"},"PeriodicalIF":0.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931728","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}

{"title":"Regulatory Axis of circMYO9B and hsa-miR-3529-5p in modulating the breast Cancer biomarker MUC1","authors":"Farnaz Nourmohammadian Dehkordi ,&nbsp;Fatemeh Chaharlang ,&nbsp;Niosha Yahyavi ,&nbsp;Sadaf Gilanian ,&nbsp;Anosha Yahyavi kalkhoran ,&nbsp;Mohamadali Naderi ,&nbsp;Maryam Yousefi ,&nbsp;Nasrin Fattahi Dolatabadi","doi":"10.1016/j.humgen.2025.201468","DOIUrl":"10.1016/j.humgen.2025.201468","url":null,"abstract":"<div><h3>Purpose</h3><div>Breast cancer (BC) is the most prevalent and lethal cancer among women worldwide. Overexpression of the MUC1 gene is observed in approximately 40 % of BC cases. Additionally, mucin-1-derived antigens are recognized as significant serum biomarkers for BC. Identifying genetic regulators of MUC1 may reveal novel pathways for managing and treating BC. This study investigates the regulatory relationship between circMYO9B, hsa-miR-3529-5p, and MUC1 expression.</div></div><div><h3>Methods</h3><div>We utilized circAtlas, CircNet, and miRWalk databases to predict interactions between circMYO9B and hsa-miR-3529-5p and between hsa-miR-3529-5p and MUC1. RNA22 and RNAhybrid-BiBiServe2 confirmed an 82 % high-binding affinity between hsa-miR-3529-5p and MUC1. Experimental validation included RT-qPCR to quantify circMYO9B, hsa-miR-3529-5p, and MUC1 expression levels. Functional assays were performed by constructing plasmids for circMYO9B, hsa-miR-3529-5p, and MUC1, transfecting them into HEK293T cells, and conducting dual luciferase reporter assays.</div></div><div><h3>Result</h3><div>Our results demonstrate that circMYO9B interacts directly with hsa-miR-3529-5p, functioning as a sponge to regulate MUC1 expression in BC. This regulatory axis involving circMYO9B and hsa-miR-3529-5p provides insights into the molecular mechanisms underlying MUC1 dysregulation. MUC1, a key BC gene and marker, may be influenced by this interaction, emphasizing its potential as a target for therapeutic and diagnostic strategies. Subsequent cell viability assays confirmed that overexpression of miR-3529-5p significantly reduced MCF7 cell survival, suggesting an increase in apoptosis.</div></div><div><h3>Discussion</h3><div>This study provides valuable insights into the molecular mechanisms underlying MUC1 regulation and emphasizes the importance of miR-3529 and circMYO9B in modulating MUC1 expression, which may have implications for targeted therapies and diagnostic strategies in breast cancer.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201468"},"PeriodicalIF":0.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044156","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}

{"title":"A systems biology approach to uncover CNV-driven lncRNA regulatory networks in HPV-associated head and neck squamous cell carcinoma","authors":"Avantika Agrawal,&nbsp;Pubali Bhattacharjee,&nbsp;Swapnil Kumar,&nbsp;Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201469","DOIUrl":"10.1016/j.humgen.2025.201469","url":null,"abstract":"<div><div>Copy number variations (CNVs) have been identified as critical contributors to head and neck squamous cell carcinoma (HNSCC) pathogenesis. Multi-omics analyses offer a comprehensive understanding of its underlying genetic complexities. Therefore, this study aims to examine the CNV-driven long non-coding RNAs (lncRNAs) influencing global regulatory triplet networks (lncRNA–miRNA–mRNA) in HPV-positive and HPV-negative HNSCC subtypes. Differential expression of miRNAs, mRNAs, and CNV-associated lncRNAs were identified using TCGA-HNSCC data. Subsequently, target prediction analyses enabled the construction of CNV-driven global triplet networks specific to HPV status. Gene Ontology (GO) analysis revealed that mRNAs in HPV-positive HNSCC were enriched in cancer-associated processes such as cell proliferation and extracellular matrix (ECM) organization. In contrast, those in HPV-negative HNSCC were primarily enriched in tissue remodeling, development, and cancer progression. KEGG pathway enrichment further supported these findings. The relationship between the CNV of lncRNA MCCC1-AS1 and its expression has revealed that there was no correlation between them in the HPV-positive HNSCC, while in the HPV-negative HNSCC, the gene expression of lncRNA MCCC1-AS1 was correlated with the CNV status. Survival analysis disclosed that the patient with a copy number gain of MCCC1-AS1 was associated with a shorter survival time, suggesting its potential as a prognostic biomarker. These findings highlight the significance of CNV-driven lncRNAs in the molecular landscape of HNSCC and suggest that MCCC1-AS1 may serve as a promising target for further investigation in diagnostic and therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201469"},"PeriodicalIF":0.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912332","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}