Human Gene最新文献

{"title":"Hippo/YAP Signaling in cataract pathogenesis: Mechanistic insights and emerging therapeutic strategies","authors":"Meraj Khan,&nbsp;Lokesh Verma","doi":"10.1016/j.humgen.2025.201522","DOIUrl":"10.1016/j.humgen.2025.201522","url":null,"abstract":"<div><div>Cataracts represent a primary cause of visual impairment, arising from the opacification of the eye's crystalline lens. These can be categorized etiologically as congenital, age-related, or secondary, and clinically as cortical or nuclear, based on the location of the opacification. The Hippo/YAP signaling pathway is a fundamental cellular mechanism that governs lens epithelial cell (LEC) behavior, and its dysregulation is a key factor in cataract formation. Abnormalities in this pathway disrupt LEC proliferation and differentiation, leading to lens opacification. The effector protein YAP plays a crucial role in lens pathology, including posterior capsule opacification (PCO) and epithelial-mesenchymal transition (EMT). To address this, current research is exploring novel therapies that target the Hippo/YAP pathway to counteract these processes. These innovative approaches include using small molecule inhibitors, such as verteporfin, to disrupt YAP's function, as well as RNA-based therapies that target non-coding RNAs like lncRNA-MIAT to suppress LEC proliferation. Furthermore, gene-editing technologies like CRISPR/Cas9 are being explored to correct genetic defects associated with cataracts, such as mutations in GJA8. These molecularly targeted interventions represent a paradigm shift in cataract management, aiming to prevent the condition and improve patient outcomes. However, thorough validation is necessary to ensure their safety and efficacy for clinical application.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201522"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790126","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":"Comprehensive in silico and in vitro studies reveal the miR-30a/CALU axis as a potential therapeutic target in colorectal cancer","authors":"Parinaz Nasri Nasrabadi ,&nbsp;Forouzandeh Mahjoubi ,&nbsp;Gilles A. Robichaud ,&nbsp;Fatemeh Masoumi ,&nbsp;Alireza Zomorodipour","doi":"10.1016/j.humgen.2025.201518","DOIUrl":"10.1016/j.humgen.2025.201518","url":null,"abstract":"<div><div>Colorectal cancer (CRC) progression involves complex molecular mechanisms that remain incompletely understood. This study investigated the expression and functional significance of calumenin (CALU) in CRC pathogenesis. Bioinformatic analyses revealed significant CALU upregulation in CRC compared to normal tissues, with expression increasing progressively from primary to metastatic tumors. Protein-protein interaction networks positioned CALU as a hub gene interacting with multiple cancer-associated proteins. Single-cell RNA sequencing revealed cell-type-specific CALU expression patterns, with the highest levels observed in tumor-derived colonic goblet cells, colonocytes, and fibroblasts. MicroRNA target prediction algorithms identified miR-30a as a potential CALU regulator, which we confirmed through luciferase reporter assays. In CRC tissues and cell lines, miR-30a expression was significantly downregulated and inversely correlated with CALU levels. Functionally, restoration of miR-30a expression in CRC cells suppressed CALU expression, inhibited proliferation, induced G0/G1 cell cycle arrest, promoted apoptosis, and reduced migration and invasion capabilities. These effects were rescued by CALU overexpression, confirming CALU as a functional target of miR-30a. Analysis of 50 paired clinical specimens supported these findings, with CALU upregulation and miR-30a downregulation correlating with poor differentiation and lymph node metastasis. Our findings introduce the miR-30a/CALU axis as a potential therapeutic target in CRC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201518"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616456","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":"Response to commentary on Livni & Skorecki, “Distinguishing between founder and host population mtDNA lineages in the Ashkenazi population”","authors":"Joseph Livni ,&nbsp;Karl Skorecki","doi":"10.1016/j.humgen.2025.201514","DOIUrl":"10.1016/j.humgen.2025.201514","url":null,"abstract":"<div><div>This document is a response to Joseph Fiaith, Commentary on Livni &amp; Skorecki, “Distinguishing between Founder and Host Population mtDNA Lineages in the Ashkenazi Population”. Human Gene 46. doi: 10.1016.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201514"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681725","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":"In-silico prediction of PCR inhibition mechanism and exploitation of bacterial EPS mediated calcium nanoparticles as PCR facilitator for efficient forensic DNA analysis","authors":"Hirak Ranjan Dash ,&nbsp;Kamayani Vajpayee ,&nbsp;Dnyaneshwar Tanpure ,&nbsp;Mithilesh Kumar Mishra ,&nbsp;Ritesh Shukla ,&nbsp;Braja Kishore Mohapatra ,&nbsp;Surajit Das","doi":"10.1016/j.humgen.2026.201539","DOIUrl":"10.1016/j.humgen.2026.201539","url":null,"abstract":"<div><div>The routine Forensic DNA analysis result is strongly influenced by the mitigation strategy employed against potential PCR inhibitors. Bacterial Extracellular Polymeric Substances (EPS) mediated Calcium Nanoparticle and EPS combination was explored to mitigate the routine DNA extraction chemicals for a successful DNA profile generation. In-silico analysis predicted Proteinase-K (−871. 2 kCal/mol) to affect Taq DNA Polymerase most adversely, followed by Chloroform (−5.2 kCal/ mol), Phenol (−4.5 kCal/ mol), SDS (−4.1 kCal/ mol), Ethanol (−3.2 kCal/ mol), and EDTA (−2.6 kCal/ mol). 150–200 nm of needle-shaped Ca NPs and EPS (1 mg/ml) combination showed a significant increase in the PCR process influenced by the inhibitor compounds tested. The EPS + Ca NPs formulation showed the amplification efficiency of the <em>CYCLO</em> gene at 1.61–4.02 times higher than the inhibitor compounds. Besides, this formulation was able to amplify the 23 autosomal STR markers simultaneously in a multiplex PCR in the presence of the inhibitor compounds. The formulation was able to mitigate the chemical contaminants and was able to generate a complete profile with a high inter-locus balance. Thus, the EPS + Ca NPs formulation is deemed to be of suitable use in mitigating the routinely used DNA extraction chemical contaminations of DNA in analyzing forensic biological samples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201539"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395082","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":"Uncovering molecular signatures and pathogenic pathways in myotonic dystrophy type 1 through bioinformatic analysis","authors":"Ali Mahmoudi ,&nbsp;Sercan Karav ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.humgen.2026.201530","DOIUrl":"10.1016/j.humgen.2026.201530","url":null,"abstract":"<div><h3>Background</h3><div>Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG repeat expansion in the DMPK gene, resulting in RNA toxicity and transcriptional dysregulation. Identifying molecular networks is crucial for finding therapeutic targets.</div></div><div><h3>Methods</h3><div>In this study, we examined gene expression profiles of fibroblasts from patients with DM1 and healthy individuals using the GSE173359 dataset. Protein-protein interaction (PPI) networks were created using STRING and Cytoscape. Functional enrichment analysis was conducted using KEGG, Reactome, and Gene Ontology. Additionally, miRNA-mRNA interactions were analyzed with TarBase, and drug-gene associations were explored for potential repurposing using DGIdb.</div></div><div><h3>Results</h3><div>A total of 358 DEGs were identified, with 182 upregulated and 176 downregulated genes. Hub genes such as Toll-Like Receptor 4 (TLR4), Vascular Cell Adhesion Molecule 1 (VCAM1), Matrix Metallopeptidase 1 (MMP1), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Secreted Phosphoprotein 1 (SPP1), and Fibroblast Growth Factor 13 (FGF13) were found to be associated with immune signaling and tissue remodeling. Enrichment analysis indicated significant activation of IL-17, TNF, and NF-κB signaling pathways, cytokine-cytokine receptor interactions, and extracellular matrix organization. Additionally, developmental processes involving HOX genes were enriched, suggesting abnormal morphogenetic signaling. miRNA analysis highlighted hsa-miR-15a-5p and hsa-miR-34a-5p as key regulators of multiple hub genes. Drug interaction analysis identified potential candidates like Eritoran (TLR4 inhibitor) and Etoricoxib (PTGS2 inhibitor) for further investigation.</div></div><div><h3>Conclusion</h3><div>This integrative bioinformatics approach offers new insights into the molecular pathology of DM1, emphasizing inflammation, Extracellular Matrix (ECM) remodeling, and developmental reprogramming as key processes. It also suggests potential miRNAs and repurposed drugs for future therapeutic approaches.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201530"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022689","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":"Multi-dataset transcriptomic study reveals key regulatory pathways and drug targets in rheumatoid arthritis","authors":"Ali Babaei-Ghaghelestany ,&nbsp;Somayeh Pashaei ,&nbsp;Reza Khodarahmi ,&nbsp;Maryam Mehrabi ,&nbsp;Masomeh Mehrabi","doi":"10.1016/j.humgen.2025.201515","DOIUrl":"10.1016/j.humgen.2025.201515","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, progressive joint destruction, and systemic complications. Despite significant advancements in RA research, the molecular mechanisms driving disease progression remain incompletely understood. This study employed an integrated bioinformatics approach to uncover differentially expressed genes (DEGs), key signaling pathways, and potential therapeutic targets in RA. Four publicly available microarray datasets (GSE56649, GSE93272, GSE110169, and GSE45291) from the NCBI Gene Expression Omnibus (GEO) were analyzed using the <em>limma</em> package in R with thresholds of |log2 fold change| &gt; 0.1 and adjusted <em>p</em>-value &lt;0.05. Common DEGs across datasets were identified by Venn diagram analysis and subjected to functional enrichment. Protein–protein interaction (PPI) networks were constructed using STRING and analyzed in Cytoscape with CytoHubba to extract hub genes. Clustering was performed with Gephi, and drug–gene interactions were explored using DGIdb. A total of 394 common DEGs were identified, significantly enriched in proteasome function, chromatin remodeling, oxidative phosphorylation, JAK-STAT signaling, and Th17 cell differentiation—pathways central to RA pathogenesis. Network analysis revealed ten hub genes (<em>PSMA4</em>, <em>HSP90AA1</em>, <em>PSMD2</em>, <em>TRIM28</em>, <em>RBBP4</em>, <em>SIRT1</em>, <em>RPL35</em>, <em>HNRNPK</em>, <em>MAPK8</em>, and <em>PSMD10</em>) as potential regulators in RA, implicated in inflammation, immune signaling, oxidative stress, and cartilage degradation. Among them, <em>HSP90AA1</em>, <em>SIRT1</em>, and <em>MAPK8</em> showed particular relevance to RA through modulation of NF-κB, STAT3, and MAPK pathways. Drug–gene interaction analysis identified 21 small molecules targeting these hub genes, highlighting opportunities for drug repurposing. Collectively, these findings provide new insights into RA pathogenesis and highlight candidate biomarkers and therapeutic targets that may support earlier diagnosis and the development of novel targeted therapies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201515"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616458","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":"Reciprocal regulation of miR-657 and IL-37 and its association with CTLA-4 dysregulation in Pediatric asthma: Diagnostic implications","authors":"Ghanyia Jasim Shanyoor ,&nbsp;Rand Moushtaq Taleb ,&nbsp;Rawan Ahmed Nijeeb ,&nbsp;Hiba Muneer Abdel Hassan Al-Khafaji ,&nbsp;Maryam Qasim Mohammed","doi":"10.1016/j.humgen.2026.201532","DOIUrl":"10.1016/j.humgen.2026.201532","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is a chronic inflammatory disease of the airways, in which dysregulation of immune mediators contributes to disease pathogenesis. Interleukin-37 (IL-37) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are key immunoregulatory molecules, while miR-657 has been implicated in modulating IL-37 expression in inflammatory conditions.</div></div><div><h3>Objectives</h3><div>This study aimed to assess the expression levels of <em>IL-37</em>, CTLA-4, and <em>miR-657</em> in asthma patients compared with healthy individuals, and to evaluate their diagnostic relevance through Receiver Operating Characteristic (ROC) curve analysis and logistic regression, without the intention of developing a predictive model or examining molecular interactions among these parameters.</div></div><div><h3>Methods</h3><div>This study included 90 participants, comprising 45 asthma patients and 45 age- and sex-matched healthy controls. Peripheral blood samples were analyzed to measure total IgE (Rate Scattering Turbidimetric Method), IL-37 mRNA expression (qRT-PCR), miR-657 levels (qRT-PCR), and circulating CTLA-4 concentrations (ELISA). Statistical evaluation involved ROC curve analysis to assess diagnostic performance and logistic regression to determine associations with asthma risk.</div></div><div><h3>Results</h3><div>Compared with healthy controls, asthma patients exhibited significantly lower <em>IL-37</em> expression (fold change: 0.82 ± 0.2 vs. 1.12 ± 0.4) and reduced serum CTLA-4 concentrations (45.67 ± 19.92 vs. 73.75 ± 26.11 ng/mL), whereas <em>miR-657</em> expression was significantly increased (fold change: 1.59 ± 0.7 vs. 1.07 ± 0.3). ROC curve analysis demonstrated that <em>IL-37</em> (AUC = 0.771), CTLA-4 (AUC = 0.807), and <em>miR-657</em> (AUC = 0.763) possess promising diagnostic accuracy, with substantial sensitivity and specificity. Logistic regression analysis confirmed that decreased <em>IL-37</em> (OR = 0.11) and CTLA-4 (OR = 0.96), as well as elevated <em>miR-657</em> (OR = 9.74), were significantly associated with increased asthma risk (overall model AUC = 0.890), supporting their relevance as diagnostic indicators.</div></div><div><h3>Conclusion</h3><div>The reciprocal regulation of miR-657 and IL-37, alongside diminished CTLA-4, points to a disrupted immunoregulatory axis in asthma. Collectively, these findings highlight the potential utility of <em>miR-657</em>, <em>IL-37</em>, and CTLA-4 as diagnostic signatures for asthma, supporting their relevance in disease assessment and monitoring.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201532"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022690","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 polymorphisms associated with type 2 diabetes in Morocco: A systematic literature review","authors":"Atmane Ait baha ,&nbsp;Zineb Kahli ,&nbsp;Hind Idrissi Hassani ,&nbsp;Mouna Habbane ,&nbsp;Sofia Semlali ,&nbsp;Otmane El Brini ,&nbsp;Bouchra Benazzouz ,&nbsp;Nawal El Ansari ,&nbsp;Omar Akhouayri","doi":"10.1016/j.humgen.2026.201531","DOIUrl":"10.1016/j.humgen.2026.201531","url":null,"abstract":"<div><div>This systematic literature review (SLR) investigated genetic polymorphisms associated with Type 2 Diabetes Mellitus (T2DM) in the Moroccan population by analyzing original research articles from multiple electronic databases, including PubMed, Scopus, ScienceDirect, Web of Science, and EBSCO. We identified studies that examined 52 genes and 90 single nucleotide polymorphisms. These polymorphisms are distributed across critical genes implicated in T2DM susceptibility. This review revealed several significant genetic associations, with <em>TCF7L2</em> emerging as the gene most strongly associated with T2DM susceptibility in the Moroccan population. Other important genes identified included <em>CYP11B2</em>, <em>FHL2</em>, <em>ADIPOQ</em>, <em>TNF-A,</em> and <em>IGF2BP2</em>, which were associated with T2DM risk to varying degrees. The analysis revealed the involvement of multiple pathways, including inflammatory processes, insulin secretion, and glucose homeostasis in T2DM pathogenesis. These findings provide a comprehensive overview of the genetic architecture underlying T2DM in the Moroccan population, offering valuable insights for future research and the potential development of personalized therapeutic approaches. This review represents a significant step toward understanding population-specific genetic factors of T2DM and their implications for clinical practice.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201531"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975980","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":"Vitamin D receptor gene polymorphisms and the risk of autism spectrum disorder (ASD): A meta-analysis","authors":"Ghasem Fakourizad ,&nbsp;Alireza Hatami ,&nbsp;Saeed Aslani ,&nbsp;Mohammad Masoud Eslami ,&nbsp;Danyal Imani ,&nbsp;Bahman Razi ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.humgen.2025.201517","DOIUrl":"10.1016/j.humgen.2025.201517","url":null,"abstract":"<div><div>Several investigations have noted to the potential link between <em>Vitamin D Receptor</em> (<em>VDR</em>) gene polymorphisms and autism spectrum disorder (ASD); however, the findings have been controversial. To find a convincing answer, we performed this meta-analysis to identify a reliable understanding for plausible association of <em>VDR</em> gene SNPs and risk of ASD susceptibility. A systematic search was performed to search for relevant studies assessing the association between the Cdx (rs11568820), TaqI (rs731236), <em>Fok</em>I (rs2228570), <em>Apa</em>I (rs7975232), and <em>Bsm</em>I (rs1544410) SNPs of the <em>VDR</em> gene and susceptibility to ASD released before January 2024. Odd Ratio (OR) and 95 % CI were used to show statistical relationship between the <em>VDR</em> gene SNPs and ASD. In the final analysis 14 studies containing 2023 ASD patients and 2008 healthy individuals were included. The comprehensive analysis revealed that the TaqI variant across all genotypes, and the <em>Fok</em>I variant in recessive, allelic, and homozygote genetic models, were associated with an increased risk of ASD. According to the findings of this meta-analysis, TaqI and FokI SNPs play a role in predisposition to ASD; however, because of limitation in sample size and geographical distribution of included studies, findings should be interpreted cautiously.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201517"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616455","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":"Integrative transcriptomic profiling of differentially expressed genes to identify potential biomarkers and repurposable therapeutic candidates in idiopathic pulmonary fibrosis","authors":"Bhavsar Mauli Chirag ,&nbsp;Potnuri Vishnu Priyanka ,&nbsp;Subhashini","doi":"10.1016/j.humgen.2026.201533","DOIUrl":"10.1016/j.humgen.2026.201533","url":null,"abstract":"<div><div>Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by irreversible lung scarring with limited therapeutic options, poor prognosis, and high mortality rate. The present study aimed to elucidate the potential diagnostic biomarkers and therapeutic targets for IPF using an integrative bioinformatics and systems biology framework. Differential gene expression analysis of publicly available transcriptomic datasets (<span><span>GSE199152</span><svg><path></path></svg></span> and <span><span>GSE199949</span><svg><path></path></svg></span>) identified key differentially expressed genes (DEGs) involved predominantly in extracellular matrix organization, immune regulation, and fibrotic signaling pathways. Construction of protein–protein interaction (PPI) networks followed by cytoHubba analysis identified five core hub genes (ITGA2, ITGB3, ITGA11, COL1A1, and COL1A2), whose diagnostic potential was evaluated in silico using receiver operating characteristic (ROC) curve analysis. To strengthen the robustness of these biomarker candidates, an independent external dataset (<span><span>GSE92592</span><svg><path></path></svg></span>) was used for validation, where all five hub genes demonstrated high AUC values, confirming their reproducible diagnostic potential across cohorts. Gene regulatory network analysis highlighted critical transcription factors (SP1, RELA, NFKB1) and microRNAs (miR-29c, miR-21, miR-155, miR-30a) regulating these hub genes, emphasizing the complex transcriptional and post-transcriptional regulation underlying IPF. In parallel, drug repurposing analysis through DrugBank data, ADMET profiling, and molecular docking identified favorable interactions between the hub proteins and both approved (Nintedanib, Pirfenidone) and investigational drugs (Omipalisib, Olitigaltin, Suplatast, Tipelukast). Notably, Omipalisib and Olitigaltin exhibited favorable binding affinities, hydrogen bond interactions, and pharmacokinetic properties, suggesting potential therapeutic value in IPF management. Collectively, this integrative transcriptomics approach provides novel insights into IPF pathogenesis and highlights potential biomarkers and therapeutic candidates that may be further validated experimentally.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201533"},"PeriodicalIF":0.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022688","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}