IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-10 DOI: 10.1016/j.gene.2025.149890

Kiarash Saleki , Miao Xue , Amirreza Mazloomi , Bradley Spencer-Dene , Abdolrahman S. Nateri

The miR-302 cluster, a key pluripotency-associated non-coding RNA, has been implicated in stem cell homeostasis and tumourigenesis. However, its regulatory mechanisms in cancers, including colorectal cancer (CRC) remain poorly understood. Here, we demonstrate that the β-catenin/TCF4 complex significantly enhances miR-302 expression through direct promoter activation in CRC cells. We hypothesized that the β-catenin/TCF4 complex directly activates the miR-302 promoter and cooperates with NANOG in a transcriptional feedback loop sustaining stem-like traits in CRC cells. Using a combination of promoter-driven luciferase reporter assays, chromatin immunoprecipitation (ChIP), and molecular dynamics simulations, we identify a regulatory axis involving Wnt signalling and the transcription factor NANOG. Our data show that individual members of the miR-302 cluster activate the NANOG promoter, while both NANOG and β-catenin/TCF4 synergistically enhance miR-302 promoter activity, suggesting the presence of a positive feedback loop. Structural simulations further elucidate the binding interactions between TCF4, NANOG, and the miR-302 promoter, corroborating our experimental observations. Together, these findings position miR-302 as a downstream effector of Wnt/β-catenin signalling and an integral component of NANOG-mediated transcriptional networks in CRC stem-like cells. This work advances our understanding of non-coding RNA regulation in cancer and highlights potential therapeutic opportunities for targeting stemness-associated pathways.

miR-302簇是一种关键的多能性相关非编码RNA，与干细胞稳态和肿瘤发生有关。然而，其在包括结直肠癌（CRC）在内的癌症中的调节机制仍然知之甚少。在这里，我们证明β-catenin/TCF4复合物通过直接启动子激活在CRC细胞中显著增强miR-302的表达。我们假设β-catenin/TCF4复合物直接激活miR-302启动子，并在维持CRC细胞干样性状的转录反馈回路中与NANOG合作。通过结合启动子驱动的荧光素酶报告子测定、染色质免疫沉淀（ChIP）和分子动力学模拟，我们确定了一个涉及Wnt信号和转录因子NANOG的调控轴。我们的数据显示，miR-302集群的单个成员激活NANOG启动子，而NANOG和β-catenin/TCF4协同增强miR-302启动子活性，表明存在正反馈回路。结构模拟进一步阐明了TCF4、NANOG和miR-302启动子之间的结合相互作用，证实了我们的实验观察。总之，这些发现表明miR-302是Wnt/β-catenin信号传导的下游效应因子，也是CRC干细胞样细胞中nanog介导的转录网络的一个组成部分。这项工作促进了我们对癌症中非编码RNA调控的理解，并强调了针对干细胞相关途径的潜在治疗机会。

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引用次数: 0

Population structure analysis of eight goat breeds based on super-genotyping-by-sequencing 基于超基因分型测序的8个山羊品种群体结构分析。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-10 DOI: 10.1016/j.gene.2025.149877

Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma

China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise F_ST revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (F_ROH = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including DCN, SEMA3D, FGF5, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., MTOR, ROBO2, PPP3CA) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.

中国拥有丰富的本土山羊资源。然而，外来品种的引进和杂交等因素导致了当地种群的减少和遗传结构的模糊。因此，对主要地方山羊种群进行遗传多样性和种群结构评估势在必行。本研究采用Super-GBS测序技术对8个山羊品种（n = 211）的遗传多样性和群体结构进行了分析，并通过选择特征分析进一步确定了与生产性状和环境适应相关的候选基因。子午岭黑山羊（ZWL）多样性最高，大足黑山羊（DZH）多样性最低。两两FST结果显示，由于地理隔离，DZH与辽宁绒山羊/内蒙绒山羊（NMC）差异较大（0.1221），而子乌岭绒山羊（ZWLH）与河西绒山羊（HXC）差异较小（0.0066），提示基因流动。种群结构划分为三个支系：DZH为独立支系，沂蒙黑山羊（YMH）与ZWL聚类，羊绒亚群多。纯合性分析（ROH）显示，DZH品种近交率升高（FROH = 0.178），而羊绒品种近交率较低（0.071 ~ 0.098）。选择性扫描鉴定出252个与羊绒性状相关的基因，包括DCN、SEMA3D、FGF5、富含TGF-β、MAPK和调节毛囊循环的昼夜节律通路。干旱适应NMC和亚热带DZH的对比扫描鉴定出372个基因（如MTOR、ROBO2、PPP3CA）参与产热、水重吸收和缺氧反应。总之，这些发现强调了人工选择和环境适应如何共同塑造山羊的基因组结构。保护应优先考虑多样性下降的种群（如ZWLH、SXC），并实施控制育种，减少近亲繁殖，从而保护农业生物多样性和可持续利用。

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引用次数: 0

NR1D1 in tumorigenesis: dual roles, mechanisms, and therapeutic targeting NR1D1在肿瘤发生中的双重作用、机制和治疗靶向。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-09 DOI: 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.

核受体亚家族1，D组，成员1 (NR1D1，也称为rev - erba)，是一个核心的昼夜节律调节因子，在癌症中起着环境依赖的双重作用，既可以作为肿瘤抑制因子，也可以作为致癌基因。本文综述了NR1D1调控主要致癌通路的现有证据：DNA修复、免疫调节(如环GMP-AMP合成酶（cGAS)-干扰素基因刺激因子（STING）通路、nod样受体家族pyrin结构域3(NLRP3)）、代谢和信号级联如PI3K/AKT、JAK/STAT。我们强调其作为预后生物标志物和治疗靶点的临床应用，重点关注具有临床前疗效的药理学调节剂。我们还批判性地讨论了靶向NR1D1的挑战及其在联合治疗中的潜力，为癌症治疗提供了新的见解。

引用次数: 0

Double minutes: exploring the formation and oncogenic roles in cancer progression 双分钟：探索癌症进展中的形成和致癌作用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-08 DOI: 10.1016/j.gene.2025.149879

Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Jahin Fairuj Oishi, Reasat Tarannum, Nusrat Zahan Rouf

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.

ecDNA是一种环状DNA，广泛存在于人类癌症，特别是晚期肿瘤中，但很少在健康细胞中检测到。以前，它们被命名为“分钟染色质体”，最终变成了“双分钟（dm）”，因为它们成对存在。由于它们的结构和表观遗传修饰，它们赋予了特定的优势，帮助它们在细胞内存活和持续存在。耐药基因或癌基因的快速扩增、染色质可及性的增加和非孟德尔遗传都对肿瘤的适应性、侵袭性和对药物或化疗的耐药性有重要作用。因此，本文旨在讨论DMs的形成、机制和维持，研究用于检测DMs的工具，并研究不同类型癌症中常见的致癌基因。最后，多年来应用的治疗方法是减少或消除肿瘤细胞中的DMs。

引用次数: 0

Functional analysis of two component signaling system in Mycobacterium tuberculosis 结核分枝杆菌双组分信号系统的功能分析。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-07 DOI: 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.

结核病是一种通过空气传播的飞沫核传播的致命传染病。病原是结核分枝杆菌，一种抗酸杆菌。耐药结核病是一项全球性挑战，特定的分枝杆菌基因与耐药有着错综复杂的关系。许多因素涉及到该病的病因学。这篇综述特别旨在研究ClpCP，一种属于AAA + 蛋白酶家族的atp酶，以及与疾病病因相关的双组分传感器系统基因。结核分枝杆菌主要依靠蛋白质降解来调节其数量和质量，这对其涉及Clp的增殖和致病性至关重要。这种双组分传感器系统包括组氨酸激酶（HK）和反应调节因子（RR），它们控制对应激情况、饥饿、营养丰富、持久性、缺氧、休眠和主要疾病发病机制的反应。在双组分体系中，共编码SenX3/RegX3、PhoP/PhoR、DosR/DosS、MtrA/MtrB、PdtaS/PdtaR等12对，以及Rv0195、Rv0260c、Rv0818、PdtaR、Rv2884、Rv3143 6个应答调控因子。PhoPR基因已被广泛研究，结核分枝杆菌（MTB）的致病性取决于PhoPR双组分调控系统（PhoR）的传感器激酶。本文将探讨与分枝杆菌生长和发病相关的基因的作用。

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引用次数: 0

Unravelling the role of Neurotrimin (NTM), a member of the IgLON family, in mild intellectual disability and anxiety-like behaviors 揭示IgLON家族成员Neurotrimin （NTM）在轻度智力残疾和焦虑样行为中的作用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-07 DOI: 10.1016/j.gene.2025.149876

Mirella Vinci , Simone Treccarichi , Pinella Failla , Antonino Musumeci , Angelo Gloria , Miriam Virgillito , Concetta Federico , Salvatore Saccone , Francesco Calì

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.

Neurotrimin (NTM) （omim# 607938）是IgLON家族的一员，与其他神经细胞粘附蛋白协同调节神经突生长、轴突束化和突触形成。在动物模型中，NTM功能的破坏与情绪学习缺陷和焦虑样行为的增加有关。在这项研究中，我们检查了一个表现为轻度智力残疾、焦虑样行为、低挫折容忍度以及广泛性张力低下的个体。三基全外显子组测序（WES）在NTM （NM_001144058）基因中发现了一个新的核苷酸插入c.788_791dup。NTM目前缺乏将其与特定疾病联系起来的MIM表型条目，并且预测其遵循常染色体显性和隐性遗传模式。根据ACMG指南，该变异被归类为致病性，在gnomAD人群中出现的频率非常低（0.000006829）。它位于一个高度保守的位点（PhyloP: 7.674）。计算机分析预测，该变异诱导转录物的无义介导的衰变（NMD），导致NTM蛋白生产的损失。然而，如果转录本逃脱NMD，插入预计会引起移码，改变262号氨基酸以外的密码子，导致Ile263、新的Asp264和265号位置的过早终止密码子（TGA）。预计该突变将破坏NTM与其他IgLON家族蛋白（OPCML、LSAMP、NEGR1和IgLON5）的同二聚化和异二聚化，无论转录物是否降解或产生截断蛋白。这些发现表明NTM功能障碍与神经发育表型之间存在潜在联系，并突出了其作为轻度认知和行为障碍候选基因的可能作用。

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引用次数: 0

Influence of sleep duration on cumulative genetic effects on obesity and related anthropometric traits among preschool children 睡眠时间对学龄前儿童肥胖及相关人体测量特征累积遗传效应的影响

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-06 DOI: 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: GRS_all, derived from all filtered SNPs; GRS_BMI, 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, GRS_all showed marginal associations with several anthropometric measures; GRS_BMI 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.

目的：本研究评估了9个参与能量稳态和应激调节的基因（FTO、CLOCK、ARNTL、CRP、IL6、NR3C1、LEP、GHRL和ADIPOQ）对儿童人体测量特征的影响，并研究了睡眠时间对这些遗传关联的影响。方法：对来自中国上海的255名学龄前儿童进行分析，并对9个候选基因的遗传变异进行测序。得到三个遗传风险评分（GRS）： GRSall，来自所有过滤的snp；GRSBMI，基于BMI GWAS参考文献中鉴定的三个snp；和uGRS5由本地识别的snp构建。采用线性回归和Firth逻辑回归来评估GRS效应，并采用分层分析来评估睡眠对GRS关联的影响。结果：在FDR校正年龄、性别和食欲后，GRSall与几个人体测量指标显示出边际相关性；GRSBMI与更多的人体特征和较小的p值有较强的相关性；和uGRS5总体上表现出最强的相关性。分层分析显示，只有在睡眠充足的儿童中，GRS关联才很明显，而在睡眠不足的儿童中，这种关联则不存在。结论：我们的研究结果表明，9个候选基因的遗传变异，特别是来自FTO、LEP和GHRL的基因变异，对人体测量特征具有累积效应。由具有适度效应的snp构建的GRS可以作为人体测量结果和肥胖风险的预测工具，而基于gwas识别的snp的GRS比基于所有符合条件的snp的GRS具有更大的预测能力。重要的是，充足的睡眠对这些遗传效应的表现至关重要，而睡眠不足可能会减弱或掩盖这些影响。这些结果强调了将睡眠作为基因研究中关键环境因素的重要性，并支持了管理儿童肥胖风险的个性化策略。

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引用次数: 0

Revealing the genetic blueprint: A transcriptomic approach to deciphering blue iris color formation in Nili-Ravi buffalo 揭示遗传蓝图：一种转录组学方法来破译Nili-Ravi水牛蓝色虹膜颜色的形成。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-06 DOI: 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.

水牛是世界范围内具有重要经济意义的牲畜，但尼利-拉维水牛蓝虹膜的遗传基础仍然难以捉摸。我们采集了两只Murrah水牛（黑色虹膜）和两只Nili-Ravi水牛（蓝色虹膜）的混合虹膜透镜样本，并进行了对端rna测序。经质量控制，获得高质量数据64.53 Gb （Q30 ≥ 89.92 %）。差异分析(DESeq2， | log2FoldChange |≥2和padj

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引用次数: 0

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] 撤回“CYP1A2*1F多态性在癌症风险中的作用：来自46个病例对照研究的荟萃分析的证据”。[基因524(2013)168-174]。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-05 DOI: 10.1016/j.gene.2025.149822

Zhong Tian , Yi-Ling Li , Lin Zhao , Chen-Liang Zhang

引用次数: 0

Core role of H19 LncRNA in gastric cancer: From tumor ecosystem reprogramming to precision therapy H19 LncRNA在胃癌中的核心作用：从肿瘤生态系统重编程到精准治疗

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-05 DOI: 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.

胃癌（GC）是世界上第五大最常见的恶性肿瘤，也是第四大癌症相关死亡原因。由于其发病隐匿，大多数患者诊断为晚期，特点是高复发，频繁转移和多药耐药，导致预后差。因此，优化治疗策略仍然是当务之急。越来越多的证据表明GC的发生和发展与编码和非编码基因的表达失调有关。其中，长链非编码rna （lncRNAs）被认为是基因表达的关键调控因子，已成为有希望的生物标志物和治疗靶点。这篇综述的重点是lncRNA H19，强调其在胃肿瘤进展中的中心分子枢纽作用。H19调节肿瘤微环境，促进侵袭和转移，重编程细胞代谢，并有助于治疗耐药。通过整合分子、细胞和临床观点，我们提供了对h19驱动的胃肿瘤发生的精细理解，并强调了其作为生物标志物和治疗靶点的潜力。这些见解为胃癌的早期诊断、个性化治疗和rna靶向治疗的发展提供了新的机会。

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引用次数: 0

Gene最新文献

Objective

Methods

Results

Conclusions