Pub Date : 2025-11-09DOI: 10.1016/j.gene.2025.149889
Zhuangwei Lv , Ruohao Yang , Jinhua Wu , Xiaoyu Shi , Ruihan Wang , Yi’ang Niu , Zhuang Qian , Junna Jiao , Yunfeng Ma
Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα), a core circadian regulator, plays context-dependent dual roles in cancer, acting as either a tumor suppressor or oncogene. This review synthesizes current evidence on NR1D1’s regulation of key oncogenic pathways: DNA repair, immunomodulation (e.g., the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, NOD-like receptor family pyrin domain containing 3(NLRP3)), metabolism, and signaling cascades such as PI3K/AKT, JAK/STAT. We highlight its clinical utility as a prognostic biomarker and therapeutic target, focusing on pharmacological modulators with demonstrated preclinical efficacy. We also critically discuss challenges in targeting NR1D1 and its potential in combination therapies, offering new insights for cancer treatment.
{"title":"NR1D1 in tumorigenesis: dual roles, mechanisms, and therapeutic targeting","authors":"Zhuangwei Lv , Ruohao Yang , Jinhua Wu , Xiaoyu Shi , Ruihan Wang , Yi’ang Niu , Zhuang Qian , Junna Jiao , Yunfeng Ma","doi":"10.1016/j.gene.2025.149889","DOIUrl":"10.1016/j.gene.2025.149889","url":null,"abstract":"<div><div>Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα), a core circadian regulator, plays context-dependent dual roles in cancer, acting as either a tumor suppressor or oncogene. This review synthesizes current evidence on NR1D1’s regulation of key oncogenic pathways: DNA repair, immunomodulation (e.g., the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, NOD-like receptor family pyrin domain containing 3(NLRP3)), metabolism, and signaling cascades such as PI3K/AKT, JAK/STAT. We highlight its clinical utility as a prognostic biomarker and therapeutic target, focusing on pharmacological modulators with demonstrated preclinical efficacy. We also critically discuss challenges in targeting NR1D1 and its potential in combination therapies, offering new insights for cancer treatment.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149889"},"PeriodicalIF":2.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495214","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}
ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.
{"title":"Double minutes: exploring the formation and oncogenic roles in cancer progression","authors":"Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Jahin Fairuj Oishi, Reasat Tarannum, Nusrat Zahan Rouf","doi":"10.1016/j.gene.2025.149879","DOIUrl":"10.1016/j.gene.2025.149879","url":null,"abstract":"<div><div>ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149879"},"PeriodicalIF":2.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487869","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}
Pub Date : 2025-11-07DOI: 10.1016/j.gene.2025.149868
Karthikeyan Sundaram , Sridhar Rathinam
Tuberculosis is a fatal infection transmitted through airborne droplet nuclei. The etiological agent is Mycobacterium tuberculosis, an acid-fast bacillus. Drug-resistant tuberculosis poses a global challenge, with specific mycobacterial genes intricately associated with drug resistance. Numerous factors are implicated in the etiology of the condition. This review specifically aims to examine ClpCP, an ATPase belonging to the AAA + protease family, and the genes of the two-component sensor system related with disease etiology. Mycobacterium TB depends significantly on protein degradation to regulate their quantity and quality, which is crucial for its proliferation and pathogenicity involving Clp. The two-component sensor system comprises histidine kinase (HK) and response regulator (RR), which governs responses to stress situations, starvation, nutritional abundance, persistence, hypoxia, dormancy, and primarily disease pathogenesis. Within the two-component system, there exist 12 pairs, including SenX3/RegX3, PhoP/PhoR, DosR/DosS, MtrA/MtrB, and PdtaS/PdtaR, alongside 6 response regulators Rv0195, Rv0260c, Rv0818, PdtaR, Rv2884, and Rv3143 encoded in the Mycobacterium tuberculosis genome. The PhoPR genes have been extensively researched, and the pathogenicity of Mycobacterium tuberculosis (MTB) is contingent upon the sensor kinase of the PhoPR two-component regulatory system, known as PhoR. This review will examine the roles of genes related to the factors associated with mycobacterial growth and pathogenesis.
{"title":"Functional analysis of two component signaling system in Mycobacterium tuberculosis","authors":"Karthikeyan Sundaram , Sridhar Rathinam","doi":"10.1016/j.gene.2025.149868","DOIUrl":"10.1016/j.gene.2025.149868","url":null,"abstract":"<div><div>Tuberculosis is a fatal infection transmitted through airborne droplet nuclei. The etiological agent is Mycobacterium tuberculosis, an acid-fast bacillus. Drug-resistant tuberculosis poses a global challenge, with specific mycobacterial genes intricately associated with drug resistance. Numerous factors are implicated in the etiology of the condition. This review specifically aims to examine ClpCP, an ATPase belonging to the AAA + protease family, and the genes of the two-component sensor system related with disease etiology. Mycobacterium TB depends significantly on protein degradation to regulate their quantity and quality, which is crucial for its proliferation and pathogenicity involving Clp. The two-component sensor system comprises histidine kinase (HK) and response regulator (RR), which governs responses to stress situations, starvation, nutritional abundance, persistence, hypoxia, dormancy, and primarily disease pathogenesis. Within the two-component system, there exist 12 pairs, including SenX3/RegX3, PhoP/PhoR, DosR/DosS, MtrA/MtrB, and PdtaS/PdtaR, alongside 6 response regulators Rv0195, Rv0260c, Rv0818, PdtaR, Rv2884, and Rv3143 encoded in the Mycobacterium tuberculosis genome. The PhoPR genes have been extensively researched, and the pathogenicity of Mycobacterium tuberculosis (MTB) is contingent upon the sensor kinase of the PhoPR two-component regulatory system, known as PhoR. This review will examine the roles of genes related to the factors associated with mycobacterial growth and pathogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"977 ","pages":"Article 149868"},"PeriodicalIF":2.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476837","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}
Neurotrimin (NTM) (OMIM #607938), a member of the IgLON family, collaborates with other neural cell adhesion proteins to regulate neurite outgrowth, axonal fasciculation, and synapse formation. Disruption of NTM function in animal models has been associated with deficits in emotional learning and increased anxiety-like behaviours. In this study, we examined an individual presenting with mild intellectual disability, anxiety-like behaviours, and low frustration tolerance, along with generalised hypotonia. Trio-based whole exome sequencing (WES) identified a de novo nucleotides insertion, c.788_791dup, in the NTM (NM_001144058) gene. NTM currently lacks a MIM phenotype entry linking it to a specific disorder, and has been predicted to follow both autosomal dominant and recessive inheritance patterns. The variant was classified as pathogenic according to ACMG guidelines and displays a very low frequency in the gnomAD population (0.000006829). It is located at a highly conserved site (PhyloP: 7.674). In-silico analysis predicted that the variant induces nonsense-mediated decay (NMD) of the transcript, resulting in loss of NTM protein production. However, if the transcript escapes NMD, the insertion is expected to cause a frameshift, altering codons beyond amino acid 262, resulting in Ile263, a novel Asp264, and a premature stop codon (TGA) in position 265. This mutation is predicted to disrupt NTM homodimerization and heterodimerization with other IgLON family proteins (OPCML, LSAMP, NEGR1, and IgLON5), regardless of whether degradation of the transcript occurs or a truncated protein is produced. These findings suggest a potential link between NTM dysfunction and neurodevelopmental phenotypes and highlight its possible role as a candidate gene for mild cognitive and behavioural disorders.
{"title":"Unravelling the role of Neurotrimin (NTM), a member of the IgLON family, in mild intellectual disability and anxiety-like behaviors","authors":"Mirella Vinci , Simone Treccarichi , Pinella Failla , Antonino Musumeci , Angelo Gloria , Miriam Virgillito , Concetta Federico , Salvatore Saccone , Francesco Calì","doi":"10.1016/j.gene.2025.149876","DOIUrl":"10.1016/j.gene.2025.149876","url":null,"abstract":"<div><div>Neurotrimin (NTM) (OMIM #<span><span>607938</span><svg><path></path></svg></span>), a member of the IgLON family, collaborates with other neural cell adhesion proteins to regulate neurite outgrowth, axonal fasciculation, and synapse formation. Disruption of NTM function in animal models has been associated with deficits in emotional learning and increased anxiety-like behaviours. In this study, we examined an individual presenting with mild intellectual disability, anxiety-like behaviours, and low frustration tolerance, along with generalised hypotonia. Trio-based whole exome sequencing (WES) identified a <em>de novo</em> nucleotides insertion, c.788_791dup, in the <em>NTM</em> (NM_001144058) gene. <em>NTM</em> currently lacks a MIM phenotype entry linking it to a specific disorder, and has been predicted to follow both autosomal dominant and recessive inheritance patterns. The variant was classified as pathogenic according to ACMG guidelines and displays a very low frequency in the gnomAD population (0.000006829). It is located at a highly conserved site (PhyloP: 7.674). <em>In-silico</em> analysis predicted that the variant induces nonsense-mediated decay (NMD) of the transcript, resulting in loss of NTM protein production. However, if the transcript escapes NMD, the insertion is expected to cause a frameshift, altering codons beyond amino acid 262, resulting in Ile263, a novel Asp264, and a premature stop codon (TGA) in position 265. This mutation is predicted to disrupt NTM homodimerization and heterodimerization with other IgLON family proteins (OPCML, LSAMP, NEGR1, and IgLON5), regardless of whether degradation of the transcript occurs or a truncated protein is produced. These findings suggest a potential link between <em>NTM</em> dysfunction and neurodevelopmental phenotypes and highlight its possible role as a candidate gene for mild cognitive and behavioural disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"976 ","pages":"Article 149876"},"PeriodicalIF":2.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145481596","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}
Pub Date : 2025-11-06DOI: 10.1016/j.gene.2025.149880
Mengna Zhang , Jianfei Lin , Shijian Liu , Yanrui Jiang , Min Meng , Qi Zhu , Guanghai Wang , Fan Jiang , Hao Mei
Objective
This study assesses the influence of genetic variations over 9 genes (FTO, CLOCK, ARNTL, CRP, IL6, NR3C1, LEP, GHRL, and ADIPOQ) involved in energy homeostasis and stress regulation on children’s anthropometric traits and examines the impact of sleep duration on these genetic associations.
Methods
We analyzed 255 preschool children from Shanghai, China, and sequenced genetic variants from the nine candidate genes. Three genetic risk scores (GRS) were derived: GRSall, derived from all filtered SNPs; GRSBMI, based on three SNPs identified in a BMI GWAS reference; and uGRS5 constructed from locally identified SNPs. Linear regression and Firth’s logistic regression were applied to assess GRS effects, and stratified analyses were performed to evaluate sleep impact on GRS associations.
Results
After adjusting for age, sex, and appetite with FDR correction, GRSall showed marginal associations with several anthropometric measures; GRSBMI demonstrated stronger associations with more anthropometric traits and smaller p-values; and uGRS5 exhibited the strongest associations overall. Stratified analyses showed that GRS associations were evident only in children with adequate sleep, while the associations were absent in the short sleep group.
Conclusions
Our findings suggest that genetic variants in the nine candidate genes, particularly those from FTO, LEP and GHRL, exert cumulative effects on anthropometric traits. GRS constructed from SNPs with modest effects can serve as a predictive tool for anthropometric outcomes and obesity risk, while GRS based on GWAS-identified SNPs can offer greater predictive power than GRS based on all eligible SNPs. Importantly, adequate sleep is essential for the manifestation of these genetic effects, whereas insufficient sleep may attenuate or mask them. These results highlight the importance of incorporating sleep as a key environmental factor in genetic studies and support personalized strategies for managing obesity risk in children.
{"title":"Influence of sleep duration on cumulative genetic effects on obesity and related anthropometric traits among preschool children","authors":"Mengna Zhang , Jianfei Lin , Shijian Liu , Yanrui Jiang , Min Meng , Qi Zhu , Guanghai Wang , Fan Jiang , Hao Mei","doi":"10.1016/j.gene.2025.149880","DOIUrl":"10.1016/j.gene.2025.149880","url":null,"abstract":"<div><h3>Objective</h3><div>This study assesses the influence of genetic variations over 9 genes (<em>FTO, CLOCK, ARNTL, CRP, IL6, NR3C1, LEP, GHRL</em>, and <em>ADIPOQ</em>) involved in energy homeostasis and stress regulation on children’s anthropometric traits and examines the impact of sleep duration on these genetic associations.</div></div><div><h3>Methods</h3><div>We analyzed 255 preschool children from Shanghai, China, and sequenced genetic variants from the nine candidate genes. Three genetic risk scores (GRS) were derived: GRS<sub>all</sub>, derived from all filtered SNPs; GRS<sub>BMI</sub>, based on three SNPs identified in a BMI GWAS reference; and uGRS<sub>5</sub> constructed from locally identified SNPs. Linear regression and Firth’s logistic regression were applied to assess GRS effects, and stratified analyses were performed to evaluate sleep impact on GRS associations.</div></div><div><h3>Results</h3><div>After adjusting for age, sex, and appetite with FDR correction, GRS<sub>all</sub> showed marginal associations with several anthropometric measures; GRS<sub>BMI</sub> demonstrated stronger associations with more anthropometric traits and smaller p-values; and uGRS<sub>5</sub> exhibited the strongest associations overall. Stratified analyses showed that GRS associations were evident only in children with adequate sleep, while the associations were absent in the short sleep group.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that genetic variants in the nine candidate genes, particularly those from <em>FTO</em>, <em>LEP</em> and <em>GHRL</em>, exert cumulative effects on anthropometric traits. GRS constructed from SNPs with modest effects can serve as a predictive tool for anthropometric outcomes and obesity risk, while GRS based on GWAS-identified SNPs can offer greater predictive power than GRS based on all eligible SNPs. Importantly, adequate sleep is essential for the manifestation of these genetic effects, whereas insufficient sleep may attenuate or mask them. These results highlight the importance of incorporating sleep as a key environmental factor in genetic studies and support personalized strategies for managing obesity risk in children.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149880"},"PeriodicalIF":2.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476843","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}
Pub Date : 2025-11-06DOI: 10.1016/j.gene.2025.149878
Dong Wang , Yixue Xu , Chaobin Qin , Xinhui Song , Hui Li , Xiaoxian Xu , Muhammad Farhan Khan , Kuiqing Cui , Zhipeng Li , Qingyou Liu
Water buffalo are economically significant livestock worldwide, yet the genetic basis of the blue iris in Nili-Ravi buffalo remains elusive. We collected mixed iris–lens samples from two Murrah buffaloes (black iris) and two Nili-Ravi buffaloes (blue iris) and performed paired-end RNA-seq. After quality control, 64.53 Gb of high-quality data (Q30 ≥ 89.92 %) were obtained. Differential analysis (DESeq2,|log2FoldChange| ≥ 2 and padj < 0.05) revealed 1,289 differentially expressed genes and 248 differentially expressed lncRNAs between blue and black irises. GO and KEGG enrichment highlighted melanogenesis, tyrosine metabolism, cysteine metabolism, and phototransduction pathways. Key differential genes related to eye development and melanin production—including the hub mRNAs KIT, MGST1, GNGT1, and TYRP1—were identified. Network analysis further showed that lncRNA MSTRG.14079.1 directly targets protein tyrosine phosphatase receptor T (PTPRT), and this interaction is significantly down-regulated in blue irises. Together, our study provides the first molecular network underlying the blue iris phenotype and establishes a theoretical basis for using this non-invasive marker to enhance breeding efficiency in buffalo.
{"title":"Revealing the genetic blueprint: A transcriptomic approach to deciphering blue iris color formation in Nili-Ravi buffalo","authors":"Dong Wang , Yixue Xu , Chaobin Qin , Xinhui Song , Hui Li , Xiaoxian Xu , Muhammad Farhan Khan , Kuiqing Cui , Zhipeng Li , Qingyou Liu","doi":"10.1016/j.gene.2025.149878","DOIUrl":"10.1016/j.gene.2025.149878","url":null,"abstract":"<div><div>Water buffalo are economically significant livestock worldwide, yet the genetic basis of the blue iris in Nili-Ravi buffalo remains elusive. We collected mixed iris–lens samples from two Murrah buffaloes (black iris) and two Nili-Ravi buffaloes (blue iris) and performed paired-end RNA-seq. After quality control, 64.53 Gb of high-quality data (Q30 ≥ 89.92 %) were obtained. Differential analysis (DESeq2,|log<sub>2</sub>FoldChange| ≥ 2 and padj < 0.05) revealed 1,289 differentially expressed genes and 248 differentially expressed lncRNAs between blue and black irises. GO and KEGG enrichment highlighted melanogenesis, tyrosine metabolism, cysteine metabolism, and phototransduction pathways. Key differential genes related to eye development and melanin production—including the hub mRNAs <em>KIT</em>, <em>MGST1</em>, <em>GNGT1</em>, and <em>TYRP1</em>—were identified. Network analysis further showed that lncRNA MSTRG.14079.1 directly targets protein tyrosine phosphatase receptor T (<em>PTPRT</em>), and this interaction is significantly down-regulated in blue irises. Together, our study provides the first molecular network underlying the blue iris phenotype and establishes a theoretical basis for using this non-invasive marker to enhance breeding efficiency in buffalo.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149878"},"PeriodicalIF":2.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476871","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}
Pub Date : 2025-11-05DOI: 10.1016/j.gene.2025.149822
Zhong Tian , Yi-Ling Li , Lin Zhao , Chen-Liang Zhang
{"title":"Retraction notice to “Role of CYP1A2*1F polymorphism in cancer risk: evidence from a meta-analysis of 46 case-control studies”. [Gene 524 (2013) 168–174]","authors":"Zhong Tian , Yi-Ling Li , Lin Zhao , Chen-Liang Zhang","doi":"10.1016/j.gene.2025.149822","DOIUrl":"10.1016/j.gene.2025.149822","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"974 ","pages":"Article 149822"},"PeriodicalIF":2.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451165","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}
Pub Date : 2025-11-05DOI: 10.1016/j.gene.2025.149871
Binbin Zeng , Jianing Zhu , Yaping Wang , Chen Gu , Wenxu Zhu , Qingqing Xu , Yuxuan Wu , Juping Chen , Yang Ai , Tianyu Zhou , Ying Lin , Lixin Hua , Yayun Qian
Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Owing to its insidious onset, most patients are diagnosed at advanced stages, marked by high recurrence, frequent metastasis, and multidrug resistance, resulting in poor outcomes. Optimizing therapeutic strategies therefore remains an urgent priority. Increasing evidence links GC initiation and progression to dysregulated expression of both coding and non-coding genes. Among them, long non-coding RNAs (lncRNAs) which recognized as pivotal regulators of gene expression have emerged as promising biomarkers and therapeutic targets. This review focuses on the lncRNA H19, highlighting its role as a central molecular hub in gastric tumor progression. H19 modulates the tumor microenvironment, promotes invasion and metastasis, reprograms cellular metabolism, and contributes to therapeutic resistance. By integrating molecular, cellular, and clinical perspectives, we provide a refined understanding of H19-driven gastric tumorigenesis and underscore its potential as a biomarker and therapeutic target. These insights offer new opportunities for early diagnosis, personalized treatment, and the development of RNA-targeted therapies for gastric cancer.
{"title":"Core role of H19 LncRNA in gastric cancer: From tumor ecosystem reprogramming to precision therapy","authors":"Binbin Zeng , Jianing Zhu , Yaping Wang , Chen Gu , Wenxu Zhu , Qingqing Xu , Yuxuan Wu , Juping Chen , Yang Ai , Tianyu Zhou , Ying Lin , Lixin Hua , Yayun Qian","doi":"10.1016/j.gene.2025.149871","DOIUrl":"10.1016/j.gene.2025.149871","url":null,"abstract":"<div><div>Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Owing to its insidious onset, most patients are diagnosed at advanced stages, marked by high recurrence, frequent metastasis, and multidrug resistance, resulting in poor outcomes. Optimizing therapeutic strategies therefore remains an urgent priority. Increasing evidence links GC initiation and progression to dysregulated expression of both coding and non-coding genes. Among them, long non-coding RNAs (lncRNAs) which recognized as pivotal regulators of gene expression have emerged as promising biomarkers and therapeutic targets. This review focuses on the lncRNA H19, highlighting its role as a central molecular hub in gastric tumor progression. H19 modulates the tumor microenvironment, promotes invasion and metastasis, reprograms cellular metabolism, and contributes to therapeutic resistance. By integrating molecular, cellular, and clinical perspectives, we provide a refined understanding of H19-driven gastric tumorigenesis and underscore its potential as a biomarker and therapeutic target. These insights offer new opportunities for early diagnosis, personalized treatment, and the development of RNA-targeted therapies for gastric cancer.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"976 ","pages":"Article 149871"},"PeriodicalIF":2.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145448759","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}
Cystic Fibrosis (CF) is increasingly diagnosed in non-European populations, including Indian children, with wide regional and ethnic variation in CFTR genotypic spectrum. This study aimed to document the CFTR genetic profile in Indian children and assess regional variability.
In a multicentric effort to strengthen CF services in India, data were collected from children with confirmed CF at AIIMS New Delhi, SKIMS Srinagar, AIIMS Jodhpur, and CMC Vellore. A stepwise testing strategy was used: initial screening for two common variants via Sanger sequencing and RFLP, followed by NGS and MLPA for broader variant detection.
Among 260 children (520chromosomes), 105 CFTR variants were identified. The most common variant, p.Phe508del, had an allele frequency of 29–34% across regions—substantially lower than the 70–80% seen in Europeans. Each region showed 4–5 common variants. The genotypic spectrum in southern/eastern India resembled that of West/Southwest Asia, while northern/western India showed similarity to Western Europe. Fourteen novel variants were detected: seven pathogenic, three likely pathogenic, and four of uncertain significance.
This is one of the most comprehensive studies to reveal region-specific CFTR variants in India. The lower prevalence of p.Phe508del and distinct genotypic patterns across regions highlight the need for customized diagnostic algorithm. There is an urgent need to evaluate the efficacy of current CFTR modulators and to explore the development of new treatments based on the unique Indian molecular spectrum.
{"title":"Profile of cystic fibrosis transmembrane conductance regulator (CFTR) gene variants across India and their variability in different geographic regions","authors":"Madhumita Roy Chowdhury , Indu Kumari , Kana Ram Jat , Nitin Dhochak , Rakesh Lodha , Sneha Varkki , Prawin Kumar , Jagdish Prasad Goyal , Javeed Iqbal Bhat , SK Kabra , Aaron Chapla , Jhuma Sankar , Madhan Kumar , Sumita Danda , Neerja Gupta , Princy Bamal , Priyanka Medhi , Ruchi Gaba , Madhulika Kabra","doi":"10.1016/j.gene.2025.149870","DOIUrl":"10.1016/j.gene.2025.149870","url":null,"abstract":"<div><div>Cystic Fibrosis (CF) is increasingly diagnosed in non-European populations, including Indian children, with wide regional and ethnic variation in CFTR genotypic spectrum. This study aimed to document the CFTR genetic profile in Indian children and assess regional variability.</div><div>In a multicentric effort to strengthen CF services in India, data were collected from children with confirmed CF at AIIMS New Delhi, SKIMS Srinagar, AIIMS Jodhpur, and CMC Vellore. A stepwise testing strategy was used: initial screening for two common variants via Sanger sequencing and RFLP, followed by NGS and MLPA for broader variant detection.</div><div>Among 260 children (520chromosomes), 105 CFTR variants were identified. The most common variant, p.Phe508del, had an allele frequency of 29–34% across regions—substantially lower than the 70–80% seen in Europeans. Each region showed 4–5 common variants. The genotypic spectrum in southern/eastern India resembled that of West/Southwest Asia, while northern/western India showed similarity to Western Europe. Fourteen novel variants were detected: seven pathogenic, three likely pathogenic, and four of uncertain significance.</div><div>This is one of the most comprehensive studies to reveal region-specific CFTR variants in India. The lower prevalence of p.Phe508del and distinct genotypic patterns across regions highlight the need for customized diagnostic algorithm. There is an urgent need to evaluate the efficacy of current CFTR modulators and to explore the development of new treatments based on the unique Indian molecular spectrum.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"976 ","pages":"Article 149870"},"PeriodicalIF":2.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470730","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}
Pub Date : 2025-11-04DOI: 10.1016/j.gene.2025.149874
Fangzhou Lu , Andy Cremers , Martijn Poeze , Martijn van Griensven , Tim J.M. Welting , Taco J. Blokhuis , Marjolein M.J. Caron
Objective
Endochondral ossification is vital for bone healing, with neutrophils playing a crucial role in the osteoimmune system. While N1 (pro-inflammatory) and N2 (regenerative) neutrophils are documented in other contexts, their role in endochondral ossification remains unclear. This study investigates their effects on ATDC5 cells.
Methods
Neutrophils from five healthy volunteers were isolated and polarized into N0 (unstimulated), N1, or N2 phenotypes. After culturing for 4 h, neutrophil-conditioned media was mixed (20 % v/v) with chondrogenic differentiation media (DM). ATDC5 cells were cultured with mixture or DM alone for 24 h, followed by continued DM culturing. On days 7 and 14, several gene expressions, ALP activity, and TGF-β3 levels were assessed.
Results
SOX9 peaked in the ATDC5 (A)/N2 group on day 7, while the A/N1 group showed the highest levels on day 14. COL2A1 was elevated in the A/N0 group on day 7. RUNX2 was higher in A/N1 and A/N2 on day 7, with A/N1 remaining elevated on day 14. MMP-13 was significantly higher in A/N1 on day 7. COL10A1 expression showed no significant changes. COL1A1 and COX2 were continually elevated in the A/N1 group. ALP activity was consistently enhanced in the A/N1 group, and TGF-β3 was lower in both A/N1 and A/N2 on day 14.
Conclusions
This study indicates that N1 neutrophils may promote chondrocyte maturation and osteogenic differentiation, while N2 neutrophils may support proliferation, hypertrophy, and maturation, providing a cell reservoir for ossification. These findings highlight their distinct roles in directing chondrogenic progenitors toward bone rather than cartilage formation.
{"title":"N1 and N2 neutrophil phenotypes may play differential roles in stimulating the endochondral ossification behaviors of ATDC5 cells","authors":"Fangzhou Lu , Andy Cremers , Martijn Poeze , Martijn van Griensven , Tim J.M. Welting , Taco J. Blokhuis , Marjolein M.J. Caron","doi":"10.1016/j.gene.2025.149874","DOIUrl":"10.1016/j.gene.2025.149874","url":null,"abstract":"<div><h3>Objective</h3><div>Endochondral ossification is vital for bone healing, with neutrophils playing a crucial role in the osteoimmune system. While N1 (pro-inflammatory) and N2 (regenerative) neutrophils are documented in other contexts, their role in endochondral ossification remains unclear. This study investigates their effects on ATDC5 cells.</div></div><div><h3>Methods</h3><div>Neutrophils from five healthy volunteers were isolated and polarized into N0 (unstimulated), N1, or N2 phenotypes. After culturing for 4 h, neutrophil-conditioned media was mixed (20 % v/v) with chondrogenic differentiation media (DM). ATDC5 cells were cultured with mixture or DM alone for 24 h, followed by continued DM culturing. On days 7 and 14, several gene expressions, ALP activity, and TGF-β3 levels were assessed.</div></div><div><h3>Results</h3><div>SOX9 peaked in the ATDC5 (A)/N2 group on day 7, while the A/N1 group showed the highest levels on day 14. COL2A1 was elevated in the A/N0 group on day 7. RUNX2 was higher in A/N1 and A/N2 on day 7, with A/N1 remaining elevated on day 14. MMP-13 was significantly higher in A/N1 on day 7. COL10A1 expression showed no significant changes. COL1A1 and COX2 were continually elevated in the A/N1 group. ALP activity was consistently enhanced in the A/N1 group, and TGF-β3 was lower in both A/N1 and A/N2 on day 14.</div></div><div><h3>Conclusions</h3><div>This study indicates that N1 neutrophils may promote chondrocyte maturation and osteogenic differentiation, while N2 neutrophils may support proliferation, hypertrophy, and maturation, providing a cell reservoir for ossification. These findings highlight their distinct roles in directing chondrogenic progenitors toward bone rather than cartilage formation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"976 ","pages":"Article 149874"},"PeriodicalIF":2.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458215","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号