BMC Medical Genomics最新文献

{"title":"Spectrum of genetic alterations in patients with peroxisome biogenesis defects in the Iranian population: a case series study.","authors":"Sheyda Khalilian, Mohadeseh Fathi, Sanaz Jamshidi, Rasoul Madannejad, Arezou Sayad, Soudeh Ghafouri-Fard, Mohammad Miryounesi","doi":"10.1186/s12920-025-02126-3","DOIUrl":"https://doi.org/10.1186/s12920-025-02126-3","url":null,"abstract":"<p><p>Peroxisomal disorders are a group of hereditary metabolic disorders that happen when peroxisomes are defective. Around 80% of individuals affected by peroxisomal disorders are classified within the spectrum of Zellweger syndromes with autosomal recessive inheritance pattern that results from mutations in one of the 13 PEX genes. Clinical exome sequencing plays a vital role in the diagnosis where the symptoms are atypical. In the current study, we used this technique to find the underlying genetic cause in 14 Iranian patients with peroxisomal disorders. PEX1 variants were detected in five patients. PEX2, PEX5, PEX6 and PEX7 variants were detected in three, one, one, and two cases, respectively. Finally, ACOX1 variants were identified in two cases. All cases except two cases were homozygote for the suspected variants in Zellweger syndrome-related genes. Two cases were compound heterozygote for variants in the PEX1 gene. In total, two novel variants were identified, including c.313 C > T (p.Gln105*) and c.961 A > T (p.Ile321Phe) in the PEX1 and ACOX1 genes, respectively. The present research expands the range of genetic variations observed in Iranian individuals diagnosed with various forms of Zellweger spectrum disorders.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"67"},"PeriodicalIF":2.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Putative function and prognostic molecular marker of mast cells in colorectal cancer.","authors":"Jiani Guo, Jie Chen, Yiting Wang, Xiaoming Bai, Haimei Feng, Siqi Sheng, Hongyu Wang, Ke Xu, Mengxi Huang, Zengjie Lei, Xiaoyuan Chu","doi":"10.1186/s12920-025-02117-4","DOIUrl":"https://doi.org/10.1186/s12920-025-02117-4","url":null,"abstract":"<p><strong>Background: </strong>The increased demand for markers for colorectal cancer (CRC) highlights the importance of investigating immune cells involved in CRC progression. This study aims to dissect the mast cells in CRC, characterize the role of mast cells in CRC development, coordinate molecular communication between mast cells and malignant cells, and construct and validate a prognostic classification model based on mast cell markers.</p><p><strong>Methods: </strong>Single-cell transcriptome data of CRC patients were extracted from GSE146771 for cell classification and annotation. The malignant cells were identified by copykat and the communication between mast cells and malignant cells was analyzed by CellChat. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis of mast cell markers were performed in the TCGA-COAD cohort to construct a prognostic classification model. qRT-PCR was performed to detect the mRNA expression of the molecules in the classification model in P815 and MC-9 cells. The co-culture experiment of MC38 and P815 cells were performed in 12-well transwell dish. Wound healing assay and Transwell assay were performed to detect cell migration and invasion.</p><p><strong>Results: </strong>10,186 high-quality cells in GSE146771 were annotated to 9 cell types. Six markers in mast cells (HDC, GATA2, ASAH1, BTBD19, TIMP1, FAM110A) were selected to construct a classification model. The high-risk score defined showed high infiltration of immunosuppressive cells, including endothelial cells, CAFs, Tregs and high angiogenesis and epithelial-mesenchymal transition (EMT) activities. In the model, HDC were abnormally low expressed in P815 cells, while BTBD19, FAM110A, GATA2, ASAH1 and TIMP1 showed excessive expression in P815 cells. Knockdown of GATA2 in the co-culture system of P815 and MC38 cells blocked cell migration and invasion.</p><p><strong>Conclusion: </strong>This study identified the cell types within CRC, elaborated the cellular functions of mast cells in CRC development and their molecular communication to coordinate malignant cells, and highlighted the molecular components and biological features that constitute promising prognostic classification model.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"65"},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients.","authors":"Anil K Giri, Jake Lin, Konstantinos Kyriakidis, Garima Tripathi, Henrikki Almusa","doi":"10.1186/s12920-025-02130-7","DOIUrl":"10.1186/s12920-025-02130-7","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by poor survival outcomes. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, monetary as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response. Here, we report the results of the first Exome-Wide Association Study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55,423 germline exonic SNPs to perform the analysis. We identified exome-wide significant (p < 9.02 × 10^- 7) associations for rs113985677 in CCIN with tamoxifen response, rs115400838 in TRMT5 with idelalisib response, rs11878277 in HDGFL2 with entinostat, and rs2229092 in LTA associated with vorinostat response. Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 in ATRAID, and rs11236938 in TSKU with the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level (p < 5 × 10^- 8). Additionally, a significant association of rs35704242 in NIBAN1 was associated with the combined response for nonchemotherapy medicines (p = 2.51 × 10^- 8), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the first EWAS to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"64"},"PeriodicalIF":2.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOSB is a key factor in the genetic link between inflammatory bowel disease and acute myocardial infarction: multiple bioinformatics analyses and validation.","authors":"Qingan Fu, Tianzhou Shen, Weihan Qiu, Yanhui Liao, Miao Yu, Yue Zhou","doi":"10.1186/s12920-025-02129-0","DOIUrl":"10.1186/s12920-025-02129-0","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory Bowel Disease (IBD), which includes Crohn's disease and ulcerative colitis, is associated with an increased risk of Acute Myocardial Infarction (AMI). The genetic mechanisms underlying this link are not well understood.</p><p><strong>Methods: </strong>We downloaded IBD and AMI-related microarray datasets from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and analyzed using enrichment analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Machine learning techniques, including LASSO, random forest, and Boruta, were employed to screen for hub genes. These genes were validated through qRT-PCR and Western blotting. Single-cell sequencing was used to confirm findings. Additionally, potential therapeutic targets were identified using the Connectivity Map (CMap) database.</p><p><strong>Results: </strong>Five key hub genes-THBD, FOSB, ADGPR3, IL1R2, and PLAUR-were identified as significantly involved in both IBD and AMI pathogenesis. A diagnostic model for AMI constructed using these hub genes demonstrated high predictive accuracy. Single-cell sequencing analysis and several potential drugs targeting these hub genes were identified, offering new therapeutic avenues.</p><p><strong>Conclusion: </strong>This study highlights the crucial role of FOSB and other hub genes in the comorbidity of IBD and AMI. The findings provide novel insights for early diagnosis and potential therapeutic strategies, emphasizing the importance of further investigation into these genetic links.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"63"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.","authors":"Benjamin L Spector, Boryana Koseva, Rebecca McLennan, Dithi Banerjee, Kamani Lankachandra, Todd Bradley, Rangaraj Selvarangan, Elin Grundberg","doi":"10.1186/s12920-025-02125-4","DOIUrl":"10.1186/s12920-025-02125-4","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts to identify factors responsible for differential COVID-19 severity include but are not limited to genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links to disease severity. However, whole epigenome analysis of the respiratory tract, the target tissue of SARS-CoV-2, remains ill-defined.</p><p><strong>Results: </strong>We interrogated the nasal methylome to identify pathophysiologic drivers in COVID-19 severity through whole genome bisulfite sequencing (WGBS) of nasal samples from COVID-19 positive individuals with severe and mild presentation of disease. We noted differential DNA methylation in intergenic regions and low methylated regions (LMRs), demonstrating the importance of distal regulatory elements in gene regulation in COVID-19 illness. Additionally, we demonstrated differential methylation of pathways implicated in immune cell recruitment and function, and the inflammatory response. We found significant hypermethylation of the FUT4 promoter implicating impaired neutrophil adhesion in severe disease. We also identified hypermethylation of ELF5 binding sites suggesting downregulation of ELF5 targets in the nasal cavity as a factor in COVID-19 phenotypic variability.</p><p><strong>Conclusions: </strong>This study demonstrated DNA methylation as a marker of the immune response to SARS-CoV-2 infection, with enhancer-like elements playing significant roles. It is difficult to discern whether this differential methylation is a predisposing factor to severe COVID-19, or if methylation differences occur in response to disease severity. These differences in the nasal methylome may contribute to disease severity, or conversely, the nasal immune system may respond to severe infection through differential immune cell recruitment and immune function, and through differential regulation of the inflammatory response.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"62"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association between non-steroidal anti-inflammatory drugs use and the risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.","authors":"Zi-He Peng, Ming-Rui Li, Min-Xin He, Jing Liu, Jia-Hao Dou, Ya-Wen Wang, Yao Dong, Chong Yan, Zi-Hao Li, Tie Chong, Zhao-Lun Li","doi":"10.1186/s12920-025-02128-1","DOIUrl":"10.1186/s12920-025-02128-1","url":null,"abstract":"<p><strong>Background: </strong>The results of earlier observational research on the relationships between the usage of non-steroidal anti-inflammatory medicines (NSAIDs) and the risk of benign prostatic hyperplasia (BPH) have been inconsistent.</p><p><strong>Methods: </strong>To assess these associations, we performed both univariable and multivariable Mendelian randomization (MR) studies. Instrumental variables (IVs) associated with exposures at the significance level (p < 5 × 10^-6) were selected from a comprehensive meta-analysis conducted by the United Kingdom Biobank (UKB). Summary data for BPH were obtained from the FinnGen consortium, which comprised 30,066 cases and 119,297 controls. Sensitivity analyses were performed to evaluate heterogeneity and pleiotropy.</p><p><strong>Results: </strong>We found evidence by univariable MR (UVMR) that genetically predicted NSAIDs use increased the risk of BPH (odds ratio [OR] per unit increase in log odds NSAIDs use: 1.164, 95% confidence interval [CI]: 1.041-1.302, p = 0.008). After controlling for inflammation in multivariable MR (MVMR), the link persisted (OR: 1.165, 95% CI: 1.049-1.293, p = 0.004). There were no indications of potential heterogeneity and pleiotropy in UVMR and MVMR analyses.</p><p><strong>Conclusion: </strong>The results of the MR estimates suggest that genetically predicted NSAIDs use may elevate the risk of BPH. This outcome prompts the imperative for deeper exploration into potential underlying mechanisms.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"60"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome sequencing, as a powerful diagnostic tool in hearing loss, reveals novel variants in PTPRQ missed by whole-exome sequencing.","authors":"Daniel Bengl, Asuman Koparir, Wahyu Eka Prastyo, Christian Remmele, Marcus Dittrich, Sophie Flandin, Waafa Shehata-Dieler, Clemens Grimm, Thomas Haaf, Michaela A H Hofrichter","doi":"10.1186/s12920-025-02122-7","DOIUrl":"10.1186/s12920-025-02122-7","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hearing loss (HL) is one of the most common congenital disorders, affecting 1-2 in 1,000 newborns. Modern genetic diagnostics using large gene panels and/or whole exome analysis (WES) can identify disease-causing mutations in 25-50 % of patients, with higher solve rates in individuals with earlier onset.</p><p><strong>Results: </strong>Here, we used whole-genome sequencing (WGS) to reanalyze 14 index patients/families who remained without genetic diagnosis by WES. We were able to identify the genetic cause of HL in 6 families ( <math><mo>∼</mo></math> 43 %). Two families were diagnosed with DFNB84A caused by compound heterozygous recessive mutations in PTPRQ. Three of the four underlying variants, including a structural variant, a deep intronic variant, and a splice variant, escaped detection by WES. Minigene assays confirmed the pathogenicity of the intronic and the splice variants. In addition, we used protein 3D structure prediction and rigid ligand docking to study the pathogenicity of variants that escape nonsense-mediated decay.</p><p><strong>Conclusion: </strong>In our study, we present four novel variants in PTPRQ, three of which were detected only by WGS. To our knowledge, we report here the first pathogenic deep intronic PTPRQ variant causing HL. Our results suggest that the mutational spectrum of PTPRQ is not well covered by standard WES and that PTPRQ-associated hearing loss may be more frequent than previously thought. WGS provides an additional layer of information in the diagnostics of HL.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"59"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe traumatic brain injury and risk for osteoporosis: a Mendelian randomization study.","authors":"Guoqiang Wang, Jiachen Wang, Dinglong Yang, Lin Liu, Peng Xu","doi":"10.1186/s12920-025-02127-2","DOIUrl":"10.1186/s12920-025-02127-2","url":null,"abstract":"<p><strong>Background: </strong>The influence of nervous system activity on bone remodeling has been widely reported. Patients with traumatic brain injury (TBI) exhibit a high incidence of osteoporosis (OP). Nevertheless, the relationship between severe TBI (sTBI) and OP remains unclear. We performed Mendelian randomization (MR) analysis to assess the potential causal relationship between sTBI and OP.</p><p><strong>Methods: </strong>Data on exposure and outcomes were acquired from genome-wide association studies (GWAS). Data on OP was obtained from UK Biobank (5,266 cases of OP and 331,893 controls). Data on sTBI was obtained from FinnGen Consortium (6,687 cases and 370,590 controls). Single nucleotide polymorphisms (SNPs) that underwent strict screening were regarded as instrumental variables. We used the inverse variance weighted (IVW), constrained maximum likelihood and model averaging (CML-MA), MR-Egger, and weighted median methods for causal effect estimation. To test the reliability of the results, sensitivity analysis was performed using Cochran's Q, leave-one-out, MR-Egger intercept, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) tests.</p><p><strong>Results: </strong>The IVW analysis indicates that sTBI and OP have a suggestive association (odds ratio [OR] = 1.004, 95% confidence interval [CI] = 1.001,1.007; p = 0.002), and no heterogeneity (Q = 11.536, p = 0.241) or directional pleiotropy was observed (egger_intercept = 7.368 × 10^- 5, p = 0.870). The robustness of the results was validated using a leave-one-out sensitivity test.</p><p><strong>Conclusion: </strong>According to the MR analysis, sTBI and OP are likely suggestively related. This finding contributes to the prevention of OP in patients with sTBI and provides genetic evidence supporting the theory that the nervous system regulates bone remodeling.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"61"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenine identification using deep learning and discriminative feature integration.","authors":"Salman Khan, Islam Uddin, Sumaiya Noor, Salman A AlQahtani, Nijad Ahmad","doi":"10.1186/s12920-025-02131-6","DOIUrl":"10.1186/s12920-025-02131-6","url":null,"abstract":"<p><p>N6-methyladenine (6 mA) is a pivotal DNA modification that plays a crucial role in epigenetic regulation, gene expression, and various biological processes. With advancements in sequencing technologies and computational biology, there is an increasing focus on developing accurate methods for 6 mA site identification to enhance early detection and understand its biological significance. Despite the rapid progress of machine learning in bioinformatics, accurately detecting 6 mA sites remains a challenge due to the limited generalizability and efficiency of existing approaches. In this study, we present Deep-N6mA, a novel Deep Neural Network (DNN) model incorporating optimal hybrid features for precise 6 mA site identification. The proposed framework captures complex patterns from DNA sequences through a comprehensive feature extraction process, leveraging k-mer, Dinucleotide-based Cross Covariance (DCC), Trinucleotide-based Auto Covariance (TAC), Pseudo Single Nucleotide Composition (PseSNC), Pseudo Dinucleotide Composition (PseDNC), and Pseudo Trinucleotide Composition (PseTNC). To optimize computational efficiency and eliminate irrelevant or noisy features, an unsupervised Principal Component Analysis (PCA) algorithm is employed, ensuring the selection of the most informative features. A multilayer DNN serves as the classification algorithm to identify N6-methyladenine sites accurately. The robustness and generalizability of Deep-N6mA were rigorously validated using fivefold cross-validation on two benchmark datasets. Experimental results reveal that Deep-N6mA achieves an average accuracy of 97.70% on the F. vesca dataset and 95.75% on the R. chinensis dataset, outperforming existing methods by 4.12% and 4.55%, respectively. These findings underscore the effectiveness of Deep-N6mA as a reliable tool for early 6 mA site detection, contributing to epigenetic research and advancing the field of computational biology.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"58"},"PeriodicalIF":2.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring diagnostic m6A regulators in primary open-angle glaucoma: insight from gene signature and possible mechanisms by which key genes function.","authors":"Xinyue Zhang, Jiawei Chen, Xiaoyu Zhou, Dengming Zhou, Li Liao, Yang Zhao, Ping Wu, Fen Nie, Zhimin Liao, Ziyan Cai, Xuanchu Duan","doi":"10.1186/s12920-025-02123-6","DOIUrl":"10.1186/s12920-025-02123-6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to interrogate the potential role of N6-methyladenosine (m6A) regulators in the process of trabecular meshwork (TM) tissue damage in patients with primary open-angle glaucoma (POAG).</p><p><strong>Methods: </strong>Firstly, the expression profile of m6A regulators in TM tissues of POAG patients was comprehensively analyzed by bioinformatics analysis; Plasmid transfection and siRNA gene interference were used to enhance or weaken the expression levels of YTHDC2 in human trabecular meshwork cells (HTMCs); Cell migration ability was detected by transwell chamber assay; Immunofluorescence staining assay was used to evaluate the expression of extracellular matrix (ECM) related proteins.</p><p><strong>Results: </strong>Through the analysis of GSE27276 database, 5 m6A regulators with different expression in POAG were screened out. The results of random forest model showed that these 5 m6A regulators exhibited diagnostic potential and were characteristic genes of POAG. All POAG samples could be effectively divided into two groups based on the expression levels of these 5 hub m6A regulators. Immune cell infiltration analysis indicated that the levels of activated CD8⁺ T cells and regulatory T cells were different in the two subtypes. HTMC oxidative stress cell model and TGF-β2 stimulation cell model were further constructed to verify the expression of the aforementioned hub m6A regulators, and it was found that YTHDC2 mRNA showed the same expression trend in both models. The silencing of YTHDC2 enhanced the migration ability of HTMCs and increased the synthesis ability of ECM. However, when YTHDC2^ΔYTH, which lacks the YTH domain, is overexpressed in HTMCs, there is no significant change in the ECM synthesis ability.</p><p><strong>Conclusions: </strong>The differentially expressed m6A regulators in TM tissues may serve as potential diagnostic biomarkers for POAG. And, in HTMCs, the expression level of YTHDC2 mRNA was changed under oxidative stress or TGF-β2 intervention, and then exerted its regulation on cell migration and ECM synthesis capability through m6A modification, which may be an important part of the disease process of POAG.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"57"},"PeriodicalIF":2.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}