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.
Methods
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.
Result
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.
Discussion
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.
{"title":"Regulatory Axis of circMYO9B and hsa-miR-3529-5p in modulating the breast Cancer biomarker MUC1","authors":"Farnaz Nourmohammadian Dehkordi , Fatemeh Chaharlang , Niosha Yahyavi , Sadaf Gilanian , Anosha Yahyavi kalkhoran , Mohamadali Naderi , Maryam Yousefi , 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":"2025-12-01","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}
Pub Date : 2025-12-01Epub Date: 2025-11-02DOI: 10.1016/j.humgen.2025.201508
Shubhrajit Barman , Senthil Kumar Ganesan
Background
Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.
Methods
We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.
Results
Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.
Conclusions
These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.
{"title":"Computational identification and structural characterization of deleterious non-synonymous SNPs in human IGF2","authors":"Shubhrajit Barman , Senthil Kumar Ganesan","doi":"10.1016/j.humgen.2025.201508","DOIUrl":"10.1016/j.humgen.2025.201508","url":null,"abstract":"<div><h3>Background</h3><div>Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.</div></div><div><h3>Methods</h3><div>We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.</div></div><div><h3>Results</h3><div>Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.</div></div><div><h3>Conclusions</h3><div>These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201508"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465870","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}
Pub Date : 2025-12-01Epub Date: 2025-11-05DOI: 10.1016/j.humgen.2025.201509
{"title":"Editorial: Application and integration of Omics data in disease biology","authors":"","doi":"10.1016/j.humgen.2025.201509","DOIUrl":"10.1016/j.humgen.2025.201509","url":null,"abstract":"","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201509"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568394","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}
NAFLD is a major cause of morbidity and mortality worldwide. The present study aims to investigate the therapeutic potential of selected lignans, including 6-hydroxy enterodiol and secoisolariciresinol, against the key molecular targets involved in the pathogenesis of the disease. A network pharmacology approach was employed to elucidate the interaction between the proteins of bioactive compounds and disease targets, while docking and density functional theory (DFT) calculations were conducted to assess the electronic properties and reactivity profiles of the ligands. GO and KEGG pathway enrichment analysis was done to understand the core targets that are involved in various biological pathways and biological functions. Furthermore, dynamic validation of the stability and conformational behavior of the protein-ligand complexes under the physiological condition was done through MM-GBSA free energy calculations, Free Energy Landscape (FEL) mapping, and Principal Component Analysis (PCA). AKT1, CASP3, and IL6 exhibited highly favorable binding free energies, which range from 75.0196 to 75.2026 kcal/mol, indicating the stability and binding of the proteins. Moreover, CASP3 exhibited a low energy gap and a high electrophilicity index, underscoring its potential as an effective electron acceptor. In conclusion, the present computational study provides substantial evidence for the efficacy of a group of peptides as natural therapies for the treatment of nonalcoholic fatty liver disease.
{"title":"Computational investigation of lignans as potential target for non-alcoholic fatty liver disease: Insights from network pharmacology, docking, DFT, and dynamics simulation analysis","authors":"Rajappan Chandra Satish Kumar , Akash Jayaraman , Ramesh Venkatachalapathy","doi":"10.1016/j.humgen.2025.201457","DOIUrl":"10.1016/j.humgen.2025.201457","url":null,"abstract":"<div><div>NAFLD is a major cause of morbidity and mortality worldwide. The present study aims to investigate the therapeutic potential of selected lignans, including 6-hydroxy enterodiol and secoisolariciresinol, against the key molecular targets involved in the pathogenesis of the disease. A network pharmacology approach was employed to elucidate the interaction between the proteins of bioactive compounds and disease targets, while docking and density functional theory (DFT) calculations were conducted to assess the electronic properties and reactivity profiles of the ligands. GO and KEGG pathway enrichment analysis was done to understand the core targets that are involved in various biological pathways and biological functions. Furthermore, dynamic validation of the stability and conformational behavior of the protein-ligand complexes under the physiological condition was done through MM-GBSA free energy calculations, Free Energy Landscape (FEL) mapping, and Principal Component Analysis (PCA). AKT1, CASP3, and IL6 exhibited highly favorable binding free energies, which range from 75.0196 to 75.2026 kcal/mol, indicating the stability and binding of the proteins. Moreover, CASP3 exhibited a low energy gap and a high electrophilicity index, underscoring its potential as an effective electron acceptor. In conclusion, the present computational study provides substantial evidence for the efficacy of a group of peptides as natural therapies for the treatment of nonalcoholic fatty liver disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201457"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749703","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}
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.
{"title":"A systems biology approach to uncover CNV-driven lncRNA regulatory networks in HPV-associated head and neck squamous cell carcinoma","authors":"Avantika Agrawal, Pubali Bhattacharjee, Swapnil Kumar, 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":"2025-12-01","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}
Sickle Cell Anemia (SCA) is a monogenic disorder characterized by significant clinical heterogeneity, much of which is modulated by fetal hemoglobin (HbF) levels. The -158C > T XmnI polymorphism (rs7482144) in the Gγ-globin gene promoter is a known genetic determinant of HbF expression. This study investigates the association of the Gγ-158C > T XmnI polymorphism with HbF levels in SCA patients from Eastern India and global evidence through a meta-analysis.
Methods
A case-control study was conducted involving 100 SCA patients and 50 healthy controls from Eastern India. Genotyping for the Gγ-158C > T XmnI polymorphism was performed using PCR-RFLP. Clinical and hematological parameters, including HbF percentage, were assessed. Genotype and allele frequencies were compared between cases and controls. A meta-analysis was performed, incorporating 591 SCA cases and 531 controls were included from 10 published studies satisfying the criteria, including the present investigation, evaluating various genetic models (T vs C, TT vs CC, TT vs CC + CT, CT vs CC, TT + CT vs CC). Heterogeneity and publication bias were assessed using standard statistical methods.
Results
SCA patients exhibited significantly higher frequencies of the T allele (76.5 %) and TT genotype (66 %) compared to controls (T allele: 37 %, TT genotype: 22 %). HbF levels were significantly elevated in TT homozygotes (21.8 ± 8.57 %) compared to CT (17.5 ± 9.51 %) and CC (13.01 ± 5.35 %) genotypes (p < 0.003). The T allele and TT genotype were strongly associated with SCA, with odds ratios (OR) of 0.18 (95 % CI: 0.11–0.30, p < 0.0001) and 0.09 (95 % CI: 0.04–0.23, p < 0.0001), respectively. Meta-analysis confirmed a significant association between the T allele and increased HbF levels in SCA across populations (T vs C: pooled OR = 0.359, 95 % CI: 0.200–0.643, p = 0.001; TT vs CC: pooled OR = 0.186, 95 % CI: 0.107–0.321, p = 0.000). Moderate heterogeneity was observed for some comparisons (I2 up to 77.6 %), but no significant publication bias was detected.
Conclusion
The Gγ-158C > T XmnI polymorphism is significantly associated with increased HbF levels and a protective effect in SCA patients, both in the Eastern Indian population and globally. These findings highlight the importance of this genetic marker for prognostication and potential therapeutic targeting in SCA.
镰状细胞性贫血（SCA）是一种单基因疾病，具有显著的临床异质性，其中大部分是由胎儿血红蛋白（HbF）水平调节的。-158C >；g γ-珠蛋白基因启动子中的T XmnI多态性（rs7482144）是已知的HbF表达的遗传决定因素。本研究探讨了Gγ-158C >；通过荟萃分析，来自东印度的SCA患者中T - XmnI多态性与HbF水平的关系以及全球证据。方法对来自印度东部的100例SCA患者和50例健康对照者进行病例对照研究。Gγ-158C >的基因分型；采用PCR-RFLP检测T XmnI多态性。评估临床和血液学参数，包括HbF百分比。比较病例与对照组的基因型和等位基因频率。我们进行了一项荟萃分析，纳入了591例SCA病例和531例对照，这些研究来自10项已发表的符合标准的研究，包括本研究，评估了各种遗传模型（T vs C, TT vs CC, TT vs CC, TT vs CC, CT vs CC, TT + CT vs CC）。采用标准统计方法评估异质性和发表偏倚。结果sca患者T等位基因频率（76.5%）和TT基因型频率（66%）明显高于对照组（T等位基因37%，TT基因型22%）。TT纯合子HbF水平（21.8±8.57%）显著高于CT（17.5±9.51%）和CC（13.01±5.35%）基因型(p <；0.003)。T等位基因和TT基因型与SCA密切相关，比值比（OR）为0.18 (95% CI: 0.11-0.30, p <；0.0001)和0.09 (95% CI: 0.04-0.23, p <；分别为0.0001)。meta分析证实T等位基因与SCA人群中HbF水平升高之间存在显著关联(T vs C：合并OR = 0.359, 95% CI: 0.200-0.643, p = 0.001；TT和CC:池或= 0.186,95%置信区间CI: 0.107 - -0.321, p = 0.000)。在一些比较中观察到中度异质性（I2高达77.6%），但未发现显著的发表偏倚。Gγ-158C >；在东印度人群和全球SCA患者中，T XmnI多态性与HbF水平升高和保护作用显著相关。这些发现强调了这种遗传标记对SCA预后和潜在治疗靶向的重要性。
{"title":"Association of Gγ-158C > T XmnI polymorphism with elevated HbF percentage in Sickle Cell Anemia patients: Evidence from a case-control study and meta-analysis","authors":"Satyabrata Meher , Atanu Kumar Thakur , Sushil Kumar Sahu , Siris Patel , Bimal Krushna Panda , Kishalaya Das , Snehadhini Dehury , Sarmila Sahoo , Mamata Pandey , Bisnu Prasad Dash","doi":"10.1016/j.humgen.2025.201462","DOIUrl":"10.1016/j.humgen.2025.201462","url":null,"abstract":"<div><h3>Background</h3><div>Sickle Cell Anemia (SCA) is a monogenic disorder characterized by significant clinical heterogeneity, much of which is modulated by fetal hemoglobin (HbF) levels. The -158C > T <em>Xmn</em>I polymorphism (rs7482144) in the Gγ-globin gene promoter is a known genetic determinant of HbF expression. This study investigates the association of the Gγ-158C > T XmnI polymorphism with HbF levels in SCA patients from Eastern India and global evidence through a meta-analysis.</div></div><div><h3>Methods</h3><div>A case-control study was conducted involving 100 SCA patients and 50 healthy controls from Eastern India. Genotyping for the Gγ-158C > T XmnI polymorphism was performed using PCR-RFLP. Clinical and hematological parameters, including HbF percentage, were assessed. Genotype and allele frequencies were compared between cases and controls. A meta-analysis was performed, incorporating 591 SCA cases and 531 controls were included from 10 published studies satisfying the criteria, including the present investigation, evaluating various genetic models (T vs C, TT vs CC, TT vs CC + CT, CT vs CC, TT + CT vs CC). Heterogeneity and publication bias were assessed using standard statistical methods.</div></div><div><h3>Results</h3><div>SCA patients exhibited significantly higher frequencies of the T allele (76.5 %) and TT genotype (66 %) compared to controls (T allele: 37 %, TT genotype: 22 %). HbF levels were significantly elevated in TT homozygotes (21.8 ± 8.57 %) compared to CT (17.5 ± 9.51 %) and CC (13.01 ± 5.35 %) genotypes (<em>p</em> < 0.003). The T allele and TT genotype were strongly associated with SCA, with odds ratios (OR) of 0.18 (95 % CI: 0.11–0.30, <em>p</em> < 0.0001) and 0.09 (95 % CI: 0.04–0.23, p < 0.0001), respectively. Meta-analysis confirmed a significant association between the T allele and increased HbF levels in SCA across populations (T vs C: pooled OR = 0.359, 95 % CI: 0.200–0.643, <em>p</em> = 0.001; TT vs CC: pooled OR = 0.186, 95 % CI: 0.107–0.321, <em>p</em> = 0.000). Moderate heterogeneity was observed for some comparisons (I<sup>2</sup> up to 77.6 %), but no significant publication bias was detected.</div></div><div><h3>Conclusion</h3><div>The Gγ-158C > T <em>Xmn</em>I polymorphism is significantly associated with increased HbF levels and a protective effect in SCA patients, both in the Eastern Indian population and globally. These findings highlight the importance of this genetic marker for prognostication and potential therapeutic targeting in SCA.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201462"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831344","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}
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.
{"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":"2025-12-01","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}
Pub Date : 2025-12-01Epub Date: 2025-10-13DOI: 10.1016/j.humgen.2025.201494
Ankur Datta , Esther Graceia Precious A , Akshata Shetty , Sridhar Raj S , George Priya Doss C
Diagnosing Pancreatic Cancer (PC) remains a formidable challenge for both clinicians and biomedical researchers due to its complex pathophysiology and late-stage detection. Although numerous investigations have elucidated key molecular pathways implicated in PC progression, this study advances the diagnostic paradigm by leveraging integrative transcriptomic analysis through sophisticated machine learning (ML) methodologies, notably LASSO regression and XGBoost. The closed-box characteristic of the XGBoost ML algorithm was resolved using the eXplainable artificial intelligence (XAI) based SHAP architecture. Data concerning gene expression profiles, mapped via microarray assays, from multiple datasets were retrieved and processed. A high-dimensional dataframe comprising 18,156 gene features for 464 patients was subjected to dimensionality reduction via LASSO regression to identify significant gene(s). The expression profiles of the 281 genes identified by LASSO were used to train the XGBoost disease classifier model, with an 80:20 train: test ratio. Conducting a 10-fold cross-validation yielded an average accuracy of 85 % for the XGBoost ML model. The SHAP framework highlighted the top gene features contributing to the decision-making of the XGBoost disease classifier model. The LASSO identified gene features were then biologically annotated to unravel the underlying mechanisms associated with PC disease. The proposed workflow, implemented in the current study, aims to enhance the existing landscape of PC diagnosis, reduce the rate of false positives typically observed with microarray-based techniques, and provide a strong foundation for computational studies with promising aspects for future cancer diagnostics and therapeutics.
{"title":"Utilizing explainable AI to decipher transcriptomic alterations in pancreatic cancer","authors":"Ankur Datta , Esther Graceia Precious A , Akshata Shetty , Sridhar Raj S , George Priya Doss C","doi":"10.1016/j.humgen.2025.201494","DOIUrl":"10.1016/j.humgen.2025.201494","url":null,"abstract":"<div><div>Diagnosing Pancreatic Cancer (PC) remains a formidable challenge for both clinicians and biomedical researchers due to its complex pathophysiology and late-stage detection. Although numerous investigations have elucidated key molecular pathways implicated in PC progression, this study advances the diagnostic paradigm by leveraging integrative transcriptomic analysis through sophisticated machine learning (ML) methodologies, notably LASSO regression and XGBoost. The closed-box characteristic of the XGBoost ML algorithm was resolved using the eXplainable artificial intelligence (XAI) based SHAP architecture. Data concerning gene expression profiles, mapped via microarray assays, from multiple datasets were retrieved and processed. A high-dimensional dataframe comprising 18,156 gene features for 464 patients was subjected to dimensionality reduction via LASSO regression to identify significant gene(s). The expression profiles of the 281 genes identified by LASSO were used to train the XGBoost disease classifier model, with an 80:20 train: test ratio. Conducting a 10-fold cross-validation yielded an average accuracy of 85 % for the XGBoost ML model. The SHAP framework highlighted the top gene features contributing to the decision-making of the XGBoost disease classifier model. The LASSO identified gene features were then biologically annotated to unravel the underlying mechanisms associated with PC disease. The proposed workflow, implemented in the current study, aims to enhance the existing landscape of PC diagnosis, reduce the rate of false positives typically observed with microarray-based techniques, and provide a strong foundation for computational studies with promising aspects for future cancer diagnostics and therapeutics.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201494"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319599","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}
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with significant metabolic, reproductive, and psychological effects. Emerging research indicates that the disruption of circadian rhythm significantly contributes to the onset and progression of PCOS, a feature that has been insufficiently addressed. This paper presents a distinctive and comprehensive exploration of how circadian discordance, through clock gene dysregulation, sleep-wake disturbances, and external factors such as shift work, contributes to the pathophysiology of the polygenic disorder known as PCOS. This review is distinctive in that it offers opportunities to synthesize knowledge in the molecular biology of insulin processes, endocrinology, and behavioral sciences concerning circadian rhythms, insulin sensitivity, glucose metabolism, regulation of reproductive hormones, and mental health outcomes, in contrast to the prior literature. The article is organized into sections that address the molecular basis of circadian imbalance, its impact on the hypothalamic-pituitary-ovarian (HPO) axis, and its psychological implications, including persistent mood disorders and cognitive impairments. Furthermore, it introduces the novel potential of chronotherapy and circadian-based lifestyle modifications as systemic therapeutic alternatives. This review advances the understanding of circadian biology in PCOS by integrating a multidisciplinary body of knowledge, addressing research gaps, and proposing a new avenue of investigation into therapeutic strategies focused on circadian alignment to improve patient outcomes in PCOS.
{"title":"Polycystic ovary syndrome and the circadian clock: Understanding the link between metabolism, hormones, and sleep","authors":"Chaitanya Sree Somala , Thirunavukarasou Anand , Konda Mani Saravanan , Damal Chandrasekar Mathangi","doi":"10.1016/j.humgen.2025.201497","DOIUrl":"10.1016/j.humgen.2025.201497","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with significant metabolic, reproductive, and psychological effects. Emerging research indicates that the disruption of circadian rhythm significantly contributes to the onset and progression of PCOS, a feature that has been insufficiently addressed. This paper presents a distinctive and comprehensive exploration of how circadian discordance, through clock gene dysregulation, sleep-wake disturbances, and external factors such as shift work, contributes to the pathophysiology of the polygenic disorder known as PCOS. This review is distinctive in that it offers opportunities to synthesize knowledge in the molecular biology of insulin processes, endocrinology, and behavioral sciences concerning circadian rhythms, insulin sensitivity, glucose metabolism, regulation of reproductive hormones, and mental health outcomes, in contrast to the prior literature. The article is organized into sections that address the molecular basis of circadian imbalance, its impact on the hypothalamic-pituitary-ovarian (HPO) axis, and its psychological implications, including persistent mood disorders and cognitive impairments. Furthermore, it introduces the novel potential of chronotherapy and circadian-based lifestyle modifications as systemic therapeutic alternatives. This review advances the understanding of circadian biology in PCOS by integrating a multidisciplinary body of knowledge, addressing research gaps, and proposing a new avenue of investigation into therapeutic strategies focused on circadian alignment to improve patient outcomes in PCOS.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201497"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362203","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}
Pub Date : 2025-12-01Epub Date: 2025-08-13DOI: 10.1016/j.humgen.2025.201464
Kajan Muneeswaran , Varuni A. de Silva , Madhubhashinee Dayabandara , Raveen Hanwella , Naduviladath Vishvanath Chandrasekharan
Antipsychotic-induced weight gain (AIWG) is a prevalent and clinically significant side effect that compromises treatment adherence and exacerbates metabolic health risks in individuals receiving antipsychotic medication. While several genetic variants have been implicated in modulating AIWG risk, their population-specific pharmacogenetic architecture remains underexplored in South Asian settings. This study investigated the associations of four SNPs from two genes, rs6265 (BDNF gene), rs1799732, rs1800497, and rs4436578 (DRD2 gene), with AIWG in a Sri Lankan schizophrenia cohort (n = 304). SNPs were genotyped via competitive amplification of differentially melting amplicons (CADMA) with high-resolution melt analysis (HRMA) and validated via the MassARRAY System. Statistical analyses, including association, and interaction analyses, were performed using the SNPstats online tool. Genotyping and association analyses revealed marginal association of rs6265 (T allele) with weight gain (OR = 3.25, 95 % CI: 0.85–12.51, p = 0.068), while a protective role for the A allele of rs1800497 was also identified (OR = 0.58, 95 % CI: 0.36–0.91, p = 0.018). This study highlights the utility of integrating genetic screening into psychiatric care to guide personalized treatment strategies and mitigate adverse drug effects in underrepresented populations.
{"title":"Selected SNPs in the BDNF and DRD2 genes and their associations with antipsychotic-induced weight gain in a Sri Lankan cohort","authors":"Kajan Muneeswaran , Varuni A. de Silva , Madhubhashinee Dayabandara , Raveen Hanwella , Naduviladath Vishvanath Chandrasekharan","doi":"10.1016/j.humgen.2025.201464","DOIUrl":"10.1016/j.humgen.2025.201464","url":null,"abstract":"<div><div>Antipsychotic-induced weight gain (AIWG) is a prevalent and clinically significant side effect that compromises treatment adherence and exacerbates metabolic health risks in individuals receiving antipsychotic medication. While several genetic variants have been implicated in modulating AIWG risk, their population-specific pharmacogenetic architecture remains underexplored in South Asian settings. This study investigated the associations of four SNPs from two genes, rs6265 (<em>BDNF</em> gene), rs1799732, rs1800497, and rs4436578 (<em>DRD2</em> gene), with AIWG in a Sri Lankan schizophrenia cohort (<em>n</em> = 304). SNPs were genotyped via competitive amplification of differentially melting amplicons (CADMA) with high-resolution melt analysis (HRMA) and validated via the MassARRAY System. Statistical analyses, including association, and interaction analyses, were performed using the SNPstats online tool. Genotyping and association analyses revealed marginal association of rs6265 (T allele) with weight gain (OR = 3.25, 95 % CI: 0.85–12.51, <em>p</em> = 0.068), while a protective role for the A allele of rs1800497 was also identified (OR = 0.58, 95 % CI: 0.36–0.91, <em>p</em> = 0.018). This study highlights the utility of integrating genetic screening into psychiatric care to guide personalized treatment strategies and mitigate adverse drug effects in underrepresented populations.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201464"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860303","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号