Human Gene最新文献

{"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":"2026-01-14","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":"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":"2026-01-14","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":"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":"2026-01-13","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}

{"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":"2026-01-10","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":"Exploring non -coding RNAs contribution to neural tube defects","authors":"Zahraa Isam Jameel","doi":"10.1016/j.humgen.2025.201528","DOIUrl":"10.1016/j.humgen.2025.201528","url":null,"abstract":"<div><div>This review paper covers the diversified role of non-coding RNAs (ncRNAs) in the formation of neural tube defects (NTDs). NTDs are a group of serious birth defects that arise when the neural tube does not close normally during the early embryonic development. Although both genetic and environmental factors are known to cause neural tube defects (NTDs), the role of non-coding RNAs (ncRNAs) in the molecular mechanisms is becoming more evident. In this article, the different kinds of ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), and their particular roles during neural tube closure will be discussed, focusing on their prospects as therapeutic targets for NTD prevention or treatment. Studies have revealed the role of specific microRNAs, such as members in the miR-17–92 and miR-100 clusters, in the regulation of essential processes, including the proliferation, differentiation, and death of neural precursor cells. The disruption of critical signaling, such as folate metabolism and planar cell polarity, affects these processes. Moreover, there has now become evidence on the role of lncRNAs and circRNAs in the interaction with chromatin-modification complexes, influencing the epigenetic profiles required during neural tube closure, and the regulation of gene expression through the ceRNA action. The developing embryo, whose ncRNA network has the disrupted ncRNA network, has an increased risk of developing the defects in the neural tubes. conclusion, NTD ncRNs represent an important area in the understanding and diagnosis of neural tube defects. The use of ncRNs, particularly some types of microRNs, long ncRNs, and circRNs, has proven that they are far from the “noise” transcribed in the genome. In fact, they play vital roles in the regulation of genes related to the closing of the neural tube. When ncRNs, including some microRNs, long ncRNs, and circRNs, malfunction, they disrupt vital signaling, resulting in an increased risk of the development of NTDs in the embryo. ncRNs link genetic risk and environment, contributing to the increased incidence that was unaccounted for. Future studies, therefore, shall focus on the use of ncRNs in the biomarkers needed in detecting the risk factors and risk of NTDs, the use of long ncRNs and circRNs, and the development of strategies in the prevention of congenital defects.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201528"},"PeriodicalIF":0.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924589","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 utero gene therapy: Pioneering diagnostic and therapeutic technologies","authors":"Shalmoli Seth ,&nbsp;Malini Sen ,&nbsp;Souvik Banerjee ,&nbsp;Ritamay Sau ,&nbsp;Somasree Ray","doi":"10.1016/j.humgen.2025.201527","DOIUrl":"10.1016/j.humgen.2025.201527","url":null,"abstract":"<div><div>Advancements in prenatal imaging, molecular diagnostics, and genetic screening have transformed the management of congenital diseases, enabling early identification and treatment in utero. These innovations facilitate medical interventions before clinical symptoms arise, improving outcomes and reducing disease severity. Advanced genetic testing of blood, tissue, and other biological samples, combined with techniques such as fluorescence in situ hybridization and chromosomal microarray analysis, allows precise detection and classification of monogenic, mitochondrial, chromosomal, and multifactorial disorders. Emerging in utero therapies, particularly gene therapy, leverage the fetus's unique developmental properties to provide targeted and minimally invasive treatment for structural and genetic abnormalities. However, key challenges remain, such as ensuring biocompatibility and achieving efficient intracellular transgene delivery. Progress in viral and non-viral delivery systems and advancements in gene editing technologies have shown potential in overcoming these obstacles, paving the way for clinical translation. Nanotechnology further enhances these efforts by providing customizable, stable platforms for stage-specific and tissue-targeted interventions, broadening the scope of successful in utero treatments. Collectively, these advances in prenatal diagnostics and therapeutic strategies present an opportunity to address congenital disorders at their origin, significantly improving longterm health outcomes and quality of life by intervening at the earliest stages of development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201527"},"PeriodicalIF":0.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of rs10414846, rs10421768, rs855791 and rs4820268 polymorphisms in iron-regulatory genes among Malaysian young adults","authors":"Jin-Rou Liew ,&nbsp;Sing-Yan Looi ,&nbsp;Keat-Wei Loo ,&nbsp;Lai-Kuan Teh","doi":"10.1016/j.humgen.2025.201526","DOIUrl":"10.1016/j.humgen.2025.201526","url":null,"abstract":"<div><div>Genetic variants involved in iron-regulatory pathways are important determinants of individual susceptibility to iron deficiency or anaemia. Genetic determinants including the hepcidin antimicrobial peptide (<em>HAMP</em>) and transmembrane serine protease 6 (<em>TMPRSS6</em>) genes play crucial roles in systemic iron regulation. This study investigated the relationship of four single nucleotide polymorphisms (SNPs) [<em>HAMP</em> rs10414846 (C &gt; T), <em>HAMP</em> rs10421768 (A &gt; G), <em>TMPRSS6</em> rs855791 (A &gt; G) and <em>TMPRSS6</em> rs4820268 (G &gt; A)] with haemoglobin (Hb), plasma hepcidin and serum iron levels among Malaysian young adults. A total of 183 unrelated participants aged 18 to 35 years were recruited. Genotyping was conducted using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR). Plasma hepcidin concentration and serum iron levels were detected using a human hepcidin ELISA kit and an iron colorimetric assay, respectively. Statistical analyses were performed with the Kruskal-Wallis and Mann-Whitney <em>U</em> tests, followed by general linear model (GLM) adjustments for covariates. Gene-gene interactions were analysed using the Pearson Chi-square (χ²) test. A significant difference was observed between <em>TMPRSS6</em> rs855791 and plasma hepcidin concentration after adjustment (<em>p</em> = 0.039), where G allele carriers exhibited lower hepcidin concentration compared with AA homozygotes. No significant differences were observed for the other polymorphisms. Linkage disequilibrium (LD) analysis revealed strong intragenic correlations within <em>HAMP</em> and <em>TMPRSS6</em>, but no intergenic association. These findings highlighted <em>TMPRSS6</em>'s regulatory role in iron homeostasis. This study provides the first population-specific evidence among Malaysian young adults, offering baseline genetic data to support future large-scale and personalised anaemia research.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201526"},"PeriodicalIF":0.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839818","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":"Promoter methylation signature of SLC16A11 gene reavels poor prognosis in head and neck squamous cell carcinoma","authors":"Sonali Awasthi ,&nbsp;Tejulal Prasad Chaurasia ,&nbsp;Narendra Verma ,&nbsp;Satakshi Chaturvedi ,&nbsp;Anuradha Kalani ,&nbsp;Sudhir Kumar Awasthi ,&nbsp;Pramod K. Yadav ,&nbsp;Abhijeet Singh ,&nbsp;Gyanendra Singh ,&nbsp;Rajeev Mishra","doi":"10.1016/j.humgen.2025.201525","DOIUrl":"10.1016/j.humgen.2025.201525","url":null,"abstract":"<div><div>Solute carrier (SLC) transporters, which are essential for transporting various metabolites such as carbohydrates, proteins, lipids, and nucleic acids, are often altered in tumor cells to meet their high energy demands. Given the critical role of the SLC transporters in driving metabolism these transporters represent a promising target for cancer therapies and the development of biomarkers to track tumor development and progression. The SLC gene family comprises 14 members, designated SLC16A1 to SLC16A14, which have been implicated in various types of cancer. Their diverse expression patterns are often associated with a poor prognosis across multiple cancers. However, the prognostic significance and mechanisms of the distinct members of the SLC16A gene family in human head and neck squamous cell carcinoma (HNSC) remain unclear. In this study, we explored the SLC16A family members in HNSC using various online genomic databases, including GEPIA2 and TIMER2, to assess the prognostic significance of SLC16A11. Our findings revealed that the expression of the SLC16A11 gene was significantly lower in HNSC tissues compared to normal tissues. We identified that hyper-methylation of the SLC16A11 promoter was associated with decreased expression levels and a poor prognosis in HNSCC, likely due to increased immune infiltration of various immune cells. This study emphasizes the potential of SLC16A11 as a prognostic marker for head and neck squamous cell carcinoma (HNSC) and identifies it as an epigenetically regulated tumor suppressor gene. Overall our research highlights need for further investigation into SLC16A11 as a key metabolic transporter and its potential application in HNSC therapeutics.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201525"},"PeriodicalIF":0.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790125","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":"Connection between epithelial-mesenchymal transition and cancer stem cells and the potential therapeutic strategies","authors":"Jingxuan Xu ,&nbsp;Jiaxin Geng ,&nbsp;Jingyuan Ma ,&nbsp;Yaofan Lu ,&nbsp;Fuyuan Ma ,&nbsp;Yuan Qin ,&nbsp;Biao Huang","doi":"10.1016/j.humgen.2025.201524","DOIUrl":"10.1016/j.humgen.2025.201524","url":null,"abstract":"<div><div>Cancer prevalence is on the rise globally. Early detection, targeted treatments, immunotherapies, and routine chemotherapies are vital for cancer management and patient survival extension, yet complete cancer eradication remains a significant challenge. The epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) are central to cancer cell metastasis, apoptosis resistance, tumor relapse, and drug resistance. This review focuses on the molecular mechanisms of EMT and CSCs, their interdependencies, the implicated signaling cascades, and the function of microRNA (miRNA) in EMT and CSC initiation regulation. EMT can endow cancer cells with mesenchymal characteristics and the capacity to transition into a CSC state; notably, CSCs can also reinforce EMT progression through secreting cytokines like transforming growth factor-β (TGF-β), forming a reciprocal regulatory loop that sustains tumor aggressiveness. These processes are intricately linked to the TGF-β, Wnt, and Notch signaling pathways, as well as miRNA expression. Advancing cancer treatment modalities and pinpointing novel therapeutic targets necessitate deeper exploration of the EMT-CSC connection. Consequently, crafting therapeutic approaches that target EMT or CSCs holds promise for enhancing cancer treatment efficacy.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201524"},"PeriodicalIF":0.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736911","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":"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":"2025-12-08","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}