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{"title":"Mechanisms and clinical implications of microRNA associations and signaling pathways in B-cell acute lymphoblastic leukemia","authors":"Amani Dhiflaoui ,&nbsp;Wassim Y. Almawi","doi":"10.1016/j.gene.2025.149730","DOIUrl":"10.1016/j.gene.2025.149730","url":null,"abstract":"<div><h3>Purpose</h3><div>This comprehensive review examines the clinical significance of microRNA (miRNA) dysregulation in B-cell acute lymphoblastic leukemia (B-ALL), bridging the gap between mechanistic understanding and clinical translation by exploring validated biomarker applications and addressing therapeutic implementation challenges in pediatric and adult populations.</div></div><div><h3>Methods</h3><div>A comprehensive literature review was conducted to assess the role of miRNA in B-ALL pathogenesis, treatment response, and clinical outcomes. Clinical and experimental findings were examined to understand the therapeutic implications of targeting miRNA pathways.</div></div><div><h3>Results</h3><div>Specific miRNA profiles differentiate B-ALL from other leukemia subtypes, predicting treatment outcomes and relapse risk with clinical significance. Significant dysregulation of key miRNAs, especially miR-155, miR-150, and members of the let-7 family, seems to influence the PI3K/AKT, JAK/STAT, NOTCH, and Wnt signaling pathways. An 8-miRNA signature achieved 78 % accuracy in predicting prednisone response in 650 pediatric patients, leading to adjustments in treatment protocols. miR-124a methylation testing showed improved 3-year event-free survival in clinical practice. miR-181a/TGF-β1 biomarkers were validated across 15 countries and integrated into international protocols. However, therapeutic applications face notable barriers, including delivery efficiency, safety concerns, and resistance mechanisms that hinder widespread implementation.</div></div><div><h3>Conclusions</h3><div>Current evidence supports the use of miRNAs as validated biomarkers for B-ALL, demonstrating a significant impact on risk stratification and personalized treatment care. Ongoing research into improved delivery systems and comprehensive safety assessments is essential for unlocking the full therapeutic potential of miRNA-based treatments for B-ALL.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149730"},"PeriodicalIF":2.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of circular RNA and N6-methyladenosine modification in colorectal cancer","authors":"Jiamei Xu ,&nbsp;Jin Liu ,&nbsp;Fengxia Huang ,&nbsp;Zhouzhou Chao ,&nbsp;Jiayao Chen ,&nbsp;Aijing Xu ,&nbsp;Hua Zhang ,&nbsp;Wei Zhu","doi":"10.1016/j.gene.2025.149684","DOIUrl":"10.1016/j.gene.2025.149684","url":null,"abstract":"<div><div>Circular RNA (circRNA) and N6-methyladenosine (m6A) methylation modification have attracted much attention in the field of cancer research. CircRNAs represent a class of covalently closed-loop non-coding RNA (ncRNA) that are abundantly expressed in the cytoplasm. These molecules exhibit remarkable evolutionary conservation and exceptional stability, making them ideal candidates for regulatory functions. These unique properties enable circRNA to play a role in colorectal cancer (CRC), including modulation of gene expression and tumor cell biology. m6A modification is one of the most common modifications of eukaryotic messenger RNA (mRNA) and ncRNA. This dynamic modification system participates in virtually all aspects of circRNA metabolism, including biogenesis, intracellular trafficking, and turnover. At the same time, the biological function of circRNA can be involved in the regulation of the expression of m6A related enzymes. This review mainly reviews the interaction between circRNA and m6A modification, with particular emphasis on and their collective impact on CRC pathogenesis and progression.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149684"},"PeriodicalIF":2.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective mechanism of LincRNA in neurodegenerative diseases","authors":"Yizhou Lin ,&nbsp;Jiarui Wang ,&nbsp;Bowen Liu ,&nbsp;Tianye Hu ,&nbsp;Jianlan Gu","doi":"10.1016/j.gene.2025.149722","DOIUrl":"10.1016/j.gene.2025.149722","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s disease , and Huntington’s disease, are characterized by progressive neuronal dysfunction and cell death associated with protein aggregation, mitochondrial dysfunction, and neuroinflammation. Since the precise pathogenesis of NDs remains unclear, current therapeutic options are limited to symptomatic relief with minimal disease-modifying effects. Emerging evidences highlight the critical regulatory roles of long non-coding RNAs (lncRNAs) in the onset and progression of NDs through epigenetic modulation, mRNA stability control, and protein scaffolding. Among these, long intergenic non-coding RNAs (lincRNAs) have attracted significant attention for their dual roles in neuroprotection and neurodegeneration. These lincRNAs modulate disease-related genes through chromatin remodeling, miRNA sponging, and stress granule formation. This review systematically analyzes lincRNA expression signatures across NDs, their mechanistic roles in protein homeostasis, and emerging therapeutic strategies including antisense oligonucleotides and CRISPR-based approaches.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149722"},"PeriodicalIF":2.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring PTX3: a promising diagnostic marker and therapeutic target in neurology","authors":"Hong Peng ,&nbsp;Lu Zhang ,&nbsp;Yufen Tang ,&nbsp;Peng Huang ,&nbsp;Senlin Luo ,&nbsp;Zhou She ,&nbsp;Yuqiong Chen ,&nbsp;Jinwen Luo ,&nbsp;Wangxin Duan ,&nbsp;Lingjuan Liu ,&nbsp;Xingfang Li ,&nbsp;Liqun Liu","doi":"10.1016/j.gene.2025.149724","DOIUrl":"10.1016/j.gene.2025.149724","url":null,"abstract":"<div><div>Pentraxin 3 (PTX3), a key member of the pentraxin (PTX) family, is a highly conserved, multifunctional soluble humoral pattern recognition molecule. It plays a pivotal regulatory role in innate immunity, infection-inflammation, tissue remodeling, and tumorigenesis. Recent research has revealed a close association between PTX3 and the pathogenesis and progression of neurological diseases. This review details the gene localization, protein domains, and high-resolution three-dimensional conformation of PTX3. It systematically explores its core functions within signaling pathways of neurological disorders, including its regulation of synaptic plasticity and neurotransmission, involvement in neuroinflammation and immune homeostasis, promotion of nervous system tumorigenesis and progression, and mediation of fibrosis and tissue repair. Furthermore, the review evaluates the clinical value of PTX3 as a potential diagnostic and prognostic biomarker for various neurological conditions (e.g., stroke, neurodegenerative diseases, central nervous system infections, gliomas, multiple sclerosis, neurotrauma, neuropsychiatric disorders, and epilepsy). It summarizes the correlation between alterations in PTX3 expression levels in bodily fluids and tissues and disease activity, severity, and prognosis. The review also discusses the therapeutic prospects of targeting PTX3, encompassing both PTX3 inhibitors and recombinant PTX3. Overall, this review aims to comprehensively delineate the multifaceted roles of PTX3 in neurological diseases, highlighting its significant potential as both a biomarker and therapeutic target. It thus provides important opportunities for developing PTX3-based diagnostic tools and innovative therapies to improve the clinical management of diverse neurological disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149724"},"PeriodicalIF":2.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“The emerging pandemic threat of H5N1: Evolutionary adaptations for human transmission, zoonotic spillovers and surveillance gaps”","authors":"Muhammad Sheharyar Bhojani,&nbsp;Muskan Fatima Bhojani","doi":"10.1016/j.gene.2025.149723","DOIUrl":"10.1016/j.gene.2025.149723","url":null,"abstract":"<div><div>The increasing zoonotic potential of highly pathogenic avian influenza (HPAI) H5N1 poses a growing threat to global public health. This review examines the molecular and evolutionary mechanisms facilitating H5N1 adaptation in mammalian hosts, focusing on genetic reassortment events, key mutations, and transmission dynamics. Recent mammalian spillover cases, including infections in mink, sea lions, felines, and cattle, suggest a weakening species barrier, with mutations such as PB2-E627K and HA-Q226L enhancing viral replication and host receptor binding affinity. Despite these concerning developments, critical gaps remain in genomic surveillance, particularly in tracking mammalian-adapted variants. Limited sequencing efforts and cross-sectoral data-sharing inefficiencies hinder early detection, increasing the risk of undetected pandemic emergence. Advances in artificial intelligence-driven predictive modeling and the development of broadly neutralizing influenza vaccines offer promising avenues for mitigation. However, a globally coordinated approach integrating real-time genomic tracking, enhanced One Health strategies, and proactive policy interventions is essential. Without immediate action, the risk of a human-adapted H5N1 strain emerging remains a pressing global concern.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149723"},"PeriodicalIF":2.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIM2 inflammasome-mediated cell pyroptosis regulates mitophagy to participates in high glucose-induced trophoblast cell damage","authors":"Huanhuan Guo ,&nbsp;Qi Duan ,&nbsp;Yuling Cao ,&nbsp;Puchu Duan ,&nbsp;Xuewen Kou ,&nbsp;Tian Cui ,&nbsp;Yanling Zhang","doi":"10.1016/j.gene.2025.149721","DOIUrl":"10.1016/j.gene.2025.149721","url":null,"abstract":"<div><div>This study aimed to elucidate the role of absent in melanoma 2 (AIM2) in high glucose (HG)-induced trophoblast injury. An <em>in vitro</em> gestational diabetes mellitus (GDM) model was established by exposing HTR-8/SVneo cells to 25 nM glucose, followed by AIM2 knockdown. Cell viability, apoptosis, migration, and invasion were evaluated using Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), wound healing, and Transwell assays, respectively. Oxidative stress markers and inflammatory cytokines were quantified <em>via</em> specific assay kits. Immunofluorescence assays detected expressions of gasdermin D (GSDMD) and microtubule-associated protein 1 light chain 3B (LC3B). Furthermore, Western blot analysis was conducted to assess proteins related to mitophagy and pyroptosis. Results demonstrated a significant upregulation of AIM2 expression upon HG stimulation in HTR-8/SVneo cells. AIM2 silencing enhanced cell viability and migration, while attenuating HG-induced apoptosis, oxidative stress, and inflammatory responses. Mechanistic investigations revealed that AIM2 knockdown inhibited pyroptosis and activated mitophagy. Rescue experiments indicated that the protective effects conferred by AIM2 silencing against HG-induced trophoblast damage were reversed by the mitophagy inhibitor Mdivi-1. Collectively, these findings indicate that AIM2 silencing alleviates HG-induced trophoblast injury by regulating pyroptosis and mitophagy, suggesting AIM2 as a potential therapeutic target for GDM-related placental dysfunction.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149721"},"PeriodicalIF":2.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential applications and future prospects of metagenomics in aquatic ecosystems","authors":"Ajaya Kumar Rout ,&nbsp;Sushree Swati Rout ,&nbsp;Anusuiya Panda ,&nbsp;Partha Sarathi Tripathy ,&nbsp;Neelesh Kumar ,&nbsp;Satya Narayan Parida ,&nbsp;Sujata Dey ,&nbsp;Soumya Shephalika Dash ,&nbsp;Bijay Kumar Behera ,&nbsp;Pramod Kumar Pandey","doi":"10.1016/j.gene.2025.149720","DOIUrl":"10.1016/j.gene.2025.149720","url":null,"abstract":"<div><div>Metagenomics plays a vital role in advancing our understanding of microbial communities and their functional contributions in various ecosystems. By directly sequencing DNA from environmental samples such as soil, water, air, and the human body. Metagenomics enables the identification of previously uncultivable or unknown microorganisms, offering key insights into their ecological functions. Beyond taxonomic classification, metagenomic analyses reveal functional genes and metabolic pathways, facilitating the discovery of enzymes, bioactive compounds, and other molecules with applications in agriculture, biotechnology, and medicine. This review discusses the broad applications of metagenomics in environmental monitoring, encompassing sample collection, high-throughput sequencing, data analysis and interpretation. We review different sequencing platforms, library preparation methods, and advanced bioinformatics tools used for quality control, sequence assembly, and both taxonomic and functional annotation. Special focus is given to the role of metagenomics in evaluating microbial responses to environmental stress, contaminant degradation, disease emergence, and climate change. The use of microbial bioindicators for aquatic ecosystem monitoring and toxicological assessments is also examined. A comprehensive evaluation of current bioinformatics pipelines is provided for their effectiveness in processing large-scale metagenomic datasets. As global environmental pressures intensify, integrative <em>meta</em>-omics approaches, including whole-genome metagenomics, will become crucial for understanding the complexity, functions, and dynamics of microbiomes in both natural and affected ecosystems.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149720"},"PeriodicalIF":2.4,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and epigenetic landscape of erectile dysfunction: a comprehensive review","authors":"Ayodeji Folorunsho Ajayi ,&nbsp;Sylvester Olateju Bolade ,&nbsp;Temitope Victor Aremu ,&nbsp;Aduragbemi Hezekiah Ayodele ,&nbsp;Oyedayo Phillips Akano","doi":"10.1016/j.gene.2025.149716","DOIUrl":"10.1016/j.gene.2025.149716","url":null,"abstract":"<div><div>Erectile Dysfunction (ED) is a multifactorial condition with significant physical, psychological, and societal impacts, affecting approximately 24.2 % of men in the United States, with prevalence increasing with age. While lifestyle factors and comorbidities such as diabetes and cardiovascular diseases are well-established contributors, emerging evidence highlights the role of genetic predisposition in ED pathogenesis. This review evaluates the genetic architecture of ED, focusing on candidate genes, genome-wide association studies (GWAS), and epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs. A comprehensive search strategy was employed, targeting peer-reviewed articles published between 2000 and 2024 from databases such as PubMed, Google Scholar, Scopus, and Web of Science. Keywords included “erectile dysfunction,” “genetic profiling,” “epigenetics,” and “GWAS.” Studies were selected based on relevance, methodological rigor, and contributions to understanding genetic and epigenetic factors in ED. Findings reveal significant associations between ED and polymorphisms in genes such as<!--> <em>NOS3</em>,<!--> <em>PDE5A</em>,<!--> <em>AR</em>, and<!--> <em>SHBG</em>, as well as epigenetic modifications influencing endothelial function and hormonal regulation. GWAS have identified loci near<!--> <em>SIM1</em> <!-->and other genes linked to vascular health and metabolic pathways. Despite advancements, limitations such as small effect sizes of genetic variants and underrepresentation of diverse populations persist. This review underscores the potential of genetic profiling to enhance early diagnosis, personalized treatment, and preventive strategies, bridging the gap between research and clinical practice in ED management.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149716"},"PeriodicalIF":2.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editor’s Corner: Interallelic Gene Conversion","authors":"Eric B. Kmiec","doi":"10.1016/j.gene.2025.149707","DOIUrl":"10.1016/j.gene.2025.149707","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149707"},"PeriodicalIF":2.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the core promoter region of bovine FTO gene: Identification and potential regulation by GR, FOXO1, C/EBPβ, and PPARα binding sites","authors":"Qing Cui ,&nbsp;Gang Wu ,&nbsp;Qianyun Chen ,&nbsp;Yubo Feng ,&nbsp;Fudong Shang ,&nbsp;Mengmeng Ni ,&nbsp;Shijun Li","doi":"10.1016/j.gene.2025.149705","DOIUrl":"10.1016/j.gene.2025.149705","url":null,"abstract":"<div><div>The <em>fat mass and obesity-associated</em> gene (FTO) critically regulates fat metabolism. The FTO protein encoded by this gene exhibits RNA demethylase activity, enabling it to regulate adipocyte differentiation and the expression of genes involved in lipid metabolism and energy homeostasis. Consequently, it exerts significant influence on the processes of fat synthesis, storage, and degradation. Research on the <em>FTO</em> gene is crucial for elucidating lipid metabolism and obesity-related mechanisms. In this study, we examined the expression patterns of the <em>FTO</em> gene in the tissues of fetal cattle and 24-month-old Guanling cattle. Bioinformatics prediction combined with dual-luciferase reporter assays identified the core promoter region of the <em>FTO</em> gene. Site-directed mutagenesis was subsequently performed to evaluate the effects of transcription factors on promoter transcriptional activity. The results demonstrated that the expression level of the <em>FTO</em> gene was significantly higher in the adipose tissue of Guanling cattle than in other tissues (<em>P</em> &lt; 0.01), with the highest expression observed in adipose tissue. Furthermore, the core promoter region of the <em>FTO</em> gene was mapped to the region spanning −1021∼−702 bp upstream of the transcription start site. Subsequent analysis of mutations in transcription factor binding sites revealed that alterations in the binding sites for <em>GR</em>, <em>FOXO1</em>, <em>C/EBPβ</em>, and <em>PPARα</em> significantly affected the transcriptional activity of the <em>FTO</em> gene (<em>P</em> &lt; 0.05). In conclusion, this study identified the specific expression pattern of the <em>FTO</em> gene in the adipose tissue of Guanling cattle and explored the regulatory roles of the core promoter region and transcription factor binding sites in modulating promoter activity. These findings aim to further elucidate the transcriptional regulatory mechanisms of the <em>FTO</em> gene in cattle.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149705"},"PeriodicalIF":2.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}