Gene最新文献

{"title":"Translating G9a epigenetics’ role: From cell machinery to cancer therapy","authors":"Filipa Moreira-Silva ,&nbsp;Catarina Macedo-Silva ,&nbsp;Carmen Jerónimo ,&nbsp;Marianna Kruithof-de Julio","doi":"10.1016/j.gene.2025.149681","DOIUrl":"10.1016/j.gene.2025.149681","url":null,"abstract":"<div><div>Aberrant epigenetic patterns, and specifically, abnormal histone methylation accumulation, are known hallmarks of cancer development and progression. Considering this mechanism, the histone methyltransferase G9a has emerged as a key player influencing several oncogenic signaling pathways. The targeted histone residue dictates its primary enzymatic role on tumor suppressor gene silencing. Nonetheless, under similar cancer-related contexts, this enzyme can also methylate non-histone proteins, mainly related to oncogenic signaling. With this, G9a further promotes a mesenchymal and stem-cell-like phenotype, ultimately driving drug resistance acquisition. However, even though G9a has been reported as an oncogenic driver in several tumor models, as is the case with prostate cancer (PCa), the specific molecular networks altered by its hyperactivation need further investigation. In this review, we provide a comprehensive overview of the epigenetic role of G9a in cancer, and specifically, in PCa, highlighting the current research status of G9a-targeted therapies. From the literature, we can conclude that while significant progress has been made in characterizing the molecular mechanisms regulated by G9a in cancer, elucidating its context-specific roles across tumor types remains a key challenge to identify potential tumor vulnerabilities. This knowledge could facilitate the rational design of targeted treatment strategies incorporating G9a inhibitors, either as monotherapy or in combination with existing standard-of-care regimens, with the potential to enhance clinical outcomes.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"968 ","pages":"Article 149681"},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729524","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":"Mitochondrial metabolism: Critical mechanisms underpinning normal hematopoietic stem cell and acute myeloid leukemia stem cell function","authors":"Huasong Yu ,&nbsp;Lin Yan","doi":"10.1016/j.gene.2025.149685","DOIUrl":"10.1016/j.gene.2025.149685","url":null,"abstract":"<div><div>AML (Acute myeloid leukemia) is an aggressive cancer of the blood and bone marrow characterized by the excessive proliferation of immature white blood cells, that disrupt normal hematopoiesis. LSCs (Leukemic stem cells) represent a subpopulation of AML cells with stem cell-like properties that drive AML initiation, progression, and relapse by evading conventional therapies and sustaining leukemic growth. Despite advances in understanding AML biology, particularly their metabolic alternations, remain poorly understood. Indeed, recent studies have shown that mitochondrial metabolism plays a pivotal role in the regulation of both normal HSCs (hematopoietic stem cells) and LSCs. In this review, we delve into the mitochondrial metabolic characteristics of normal HSCs to provide comprehensive background knowledge. Subsequently, we thoroughly analyze how the distinctive metabolic features of LSCs, highlighting the impact of these differences on cell function and survival. We also investigate the unique mechanisms of drug resistance in LSCs, explaining how these mechanisms enhance the survival of LSCs in the face of conventional treatments. Finally, we discuss emerging therapeutic strategies targeting the mitochondrial metabolism of LSCs in AML, and we discuss prospective therapeutic strategies and future research directions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149685"},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729522","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":"Genes involved in lipid, carbohydrate and protein metabolic processes located in QTL regions affecting pork meat flavor","authors":"Paola Di Gregorio,&nbsp;Giulia Grassi,&nbsp;Anna Maria Perna,&nbsp;Emilio Sabia,&nbsp;Emilia Langella,&nbsp;Adriana Di Trana,&nbsp;Ada Braghieri","doi":"10.1016/j.gene.2025.149679","DOIUrl":"10.1016/j.gene.2025.149679","url":null,"abstract":"<div><div>Pork flavor is a complex trait whose variability depends on both genetic and environmental factors affecting quantity and quality of carbohydrates, proteins and lipids present in meat. In the last twenty years, 99 Quantitative Trait Loci (QTLs) associated with the variability of the different pork flavor traits (Flavor score, Umami flavor, Overall liking, Juiciness score, Oiliness and Off-flavor score) were identified with different coverage percentages across all <em>Sus scrofa</em> chromosomes. In this review we summarize the available data on QTLs affecting pork flavor and update their location according to the latest version (11.1) of Sscrofa Genome Assembly. Furthermore, by means of Gene Ontology (GO) analysis of genes located in these QTL regions, we identified 107 genes involved in lipid, protein and carbohydrate metabolic processes, which could be considered as candidate genes affecting the variability of flavor traits.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149679"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704064","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":"Fatty acid desaturase 2 (FAD2) is functionally involved in regulation of synthesis of fatty acid derivatives in Chrysanthemum indicum var. aromaticum","authors":"Wenjie Gao ,&nbsp;Yunjuan Liang ,&nbsp;Xingran Kou ,&nbsp;Qinfei Ke ,&nbsp;Feng Chen ,&nbsp;Guiling Liu ,&nbsp;Qingran Meng","doi":"10.1016/j.gene.2025.149680","DOIUrl":"10.1016/j.gene.2025.149680","url":null,"abstract":"<div><div>The fatty acid desaturase 2 (<em>FAD2</em>) is an important functional gene in the fatty acid metabolism pathway of aromatic plants, which can significantly affect the biosynthesis of volatile compounds and the aroma characteristics. However, the possible mechanism of action of <em>FAD2</em> in <em>Chrysanthemum indicum</em> var. <em>aromaticum</em> (<em>Ci.</em> var. <em>aromaticum</em>) is still unclear at present. In this study, the open reading frame (ORF) sequence of <em>FAD2</em> (<em>CiFAD2</em>) was cloned from <em>Ci.</em> var. <em>aromaticum</em>, and it was heterologously transferred into the model plant tobacco by constructing a plant expression vector for overexpression. Then, the changes of volatiles content and species in the leaves of transgenic tobacco overexpressing <em>CiFAD2</em> were analyzed by headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC–MS). Results showed that compared with wild-type (WT) and empty vector (EV) tobacco, tobacco plants overexpressing <em>CiFAD2</em> had a slightly delayed flowering time, darker leaf color, and smaller leaf area; the contents of terpenes increased as well as the types of alcohols and aldehydes, and new ketones were detected. Quantitative real-time PCR (qRT-PCR) results showed that the expression levels of key enzyme genes (<em>ADH</em>, <em>AOS</em>, <em>KCS</em>) in the fatty acid metabolic pathway in transgenic tobacco were all increased. This study provided data support for the potential role of <em>CiFAD2</em> in the biosynthesis process of volatile/aroma compounds in <em>Ci.</em> var. <em>aromaticum</em>, which may be applicable for cultivating new types of chrysanthemum varieties with aromatic characteristics.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149680"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704163","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":"Genome-wide identification, expression profiling, and functional analysis of sugar transporter family genes in Diaphorina citri","authors":"Cuiting Liu ,&nbsp;Xueming Cai ,&nbsp;Xinyi Xie ,&nbsp;Huiyin Hu ,&nbsp;Rui Tang ,&nbsp;Jintian Lin ,&nbsp;Zhongzhen Wu ,&nbsp;Benshui Shu","doi":"10.1016/j.gene.2025.149678","DOIUrl":"10.1016/j.gene.2025.149678","url":null,"abstract":"<div><div>Sugar transporters (STs) are important proteins responsible for the movement of sugar through the cell membrane and play pivotal roles in the growth, development, and osmoregulation of phloem-feeding hemipterans. However, information about STs in the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), remains unknown. In this study, a total of 61 STs were identified according to the genome and transcriptome analysis of D. citri. All the ST genes have complete open reading frames (ORFs), and most of them have 12 transmembrane regions. Chromosome localization and phylogenetic tree analysis found several expansions occurred in the ST gene family. The developmental stage- and tissue-specific expression patterns of <em>ST</em>s were characterized. Besides, feeding with different sugars and host plants altered the expression level of the top ten expressed genes in the midgut of D. citri. Furthermore, RNAi against <em>DcST16</em>, <em>DcST38</em>, <em>DcST52</em>, and <em>DcST56</em> induced significant mortality in <em>D. citri</em> adults. Moreover, the swollen abdomen phenotype was observed in the adults with siRNA-<em>DcST56</em> treatment. These findings lay the foundation for further function analyses of STs in D. citri.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149678"},"PeriodicalIF":2.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695089","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":"Association between the rs2279238 and rs12221497 of the LXRA gene variants and diabetic retinopathy in the Slovenian cohort","authors":"Emin Grbić ,&nbsp;Jernej Letonja ,&nbsp;Mojca Globočnik Petrovič ,&nbsp;Izabella Karska-Basta ,&nbsp;Ines Cilenšek ,&nbsp;Danijel Petrovič","doi":"10.1016/j.gene.2025.149665","DOIUrl":"10.1016/j.gene.2025.149665","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate whether the rs2279238 and rs12221497 variants in the liver X receptor alpha (<em>LXRA</em>) gene are associated with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Considering the involvement of LXRA in lipid metabolism and inflammatory pathways, we hypothesized that these genetic variants might participate in the pathogenesis of DR.</div></div><div><h3>Methods</h3><div>1554 unrelated Caucasians who had type 2 diabetes mellitus (T2DM) for more than 10 years were included. Patients were divided into two groups: the cases (with DR, 577 subjects) and the control group (without DR, 977 subjects). Genetic analysis was performed using the KASPar assay.</div></div><div><h3>Results</h3><div>We found a significant association between the rs2279238 variant and DR. The participants with the TT or TC genotype were more likely to have DR in comparison with the CC genotype according to the dominant model of inheritance (95 % OR: 1.35 (1.05–1.74), p = 0.028). We did not find an association between the rs12221497 variant and DR.</div></div><div><h3>Conclusions</h3><div>The rs2279238 variant in the <em>LXRA</em> gene is significantly associated with diabetic retinopathy (DR) in Caucasians with T2DM. Individuals carrying the TT or TC genotype have a higher risk of developing DR compared to those with the CC genotype. However, no association was found between the rs12221497 variant and DR.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149665"},"PeriodicalIF":2.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679153","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":"Dora, a key component of target-directed miRNA degradation, is essential for local genomic amplification in Drosophila ovarian follicle cells","authors":"Natalia Akulenko ,&nbsp;Oxana Olenkina ,&nbsp;Elena Mikhaleva ,&nbsp;Sofya Marfina ,&nbsp;Anastasia Krylova ,&nbsp;Stepan Toshchakov ,&nbsp;Sergei Ryazansky","doi":"10.1016/j.gene.2025.149677","DOIUrl":"10.1016/j.gene.2025.149677","url":null,"abstract":"<div><div>The ubiquitin ligase receptor Dora, the <em>Drosophila</em> homolog of ZSWIM8, is a key component of the target-directed microRNA degradation (TDMD) pathway. Previous studies have implicated TDMD – and, consequently, ZSWIM8/Dora – in various developmental processes. Here, we investigate the role Dora plays in <em>Drosophila</em> oogenesis, focusing on ovarian somatic cells. We generated a fly strain with an endogenously tagged Dora protein and observed its presence in both germline and somatic follicular cells of the ovaries. Somatic knockdown of <em>dora</em> revealed its essential role in normal eggshell formation. Specifically, Dora loss led to reduced chorion and vitelline transcript levels and decreased chorion gene amplification, both of which are critical for eggshell protein production. Somatic depletion of Dora reduces the Cut protein levels but did not affect the abundance of other known regulators of eggshell formation, including Ttk69, miR-7 or miR-318 indicating that Dora functions independently of these pathways. Although a direct link between TDMD and chorion eggshell development remains to be confirmed, our findings clearly highlight Dora as a critical regulator in this process. These results pave the way for further investigation into the specific role of TDMD and provide new insights into the regulatory mechanisms underlying animal oogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149677"},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662403","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":"Oxidative stress-related gene PRXL2A may participate in the occurrence and development of steroid-induced osteonecrosis of the femoral head by regulating osteoclast differentiation: A multi-omics analysis","authors":"Weifeng Li ,&nbsp;Hongduo Lu ,&nbsp;Yinuo Fan ,&nbsp;Yantong Luo ,&nbsp;Siyi Wu ,&nbsp;Liang Mo ,&nbsp;Benlu Chen ,&nbsp;Changbo Cheng ,&nbsp;Zhiming Wei ,&nbsp;Hanjun Fang ,&nbsp;Yuhao Liu ,&nbsp;Chi Zhou ,&nbsp;Zhaoguang Li ,&nbsp;Zeqing Huang ,&nbsp;Zhenqiu Chen","doi":"10.1016/j.gene.2025.149676","DOIUrl":"10.1016/j.gene.2025.149676","url":null,"abstract":"<div><h3>Objectives</h3><div>Steroid-induced osteonecrosis of the femoral head (SIONFH) represents a global therapeutic challenge, and its pathogenesis requires in-depth investigation. While oxidative stress is recognized as a critical contributor to SIONFH, the underlying mechanism remains incompletely elucidated.</div></div><div><h3>Methods</h3><div>In this study, multi-omics analysis of clinical specimens was performed to screen for oxidative stress-related molecules in SIONFH and identify hub molecules among them. Subsequently, the functional significance of these hub molecules was validated via Gene Ontology (GO) analysis and both in vitro and in vivo experiments. Furthermore, in vitro and in vivo experiments were conducted to further confirm the correlations between hub molecules, oxidative stress, and osteoclast differentiation.</div></div><div><h3>Results</h3><div>RNA-seq analysis identified 1,107 differentially expressed genes, with PRXL2A designated as an oxidative stress-related hub gene. Subsequent protein DIA analysis detected 139 differentially expressed proteins, further confirming PRXL2A as an oxidative stress-associated hub protein. Functional exploration revealed that PRXL2A is involved in biological processes such as oxidative stress and osteoclast differentiation. When antioxidants were applied to osteoclasts, results from TRAP staining, RT-PCR, and other assays indicated that PRXL2A expression decreased with elevated oxidative stress and also declined as osteoclast differentiation increased. Finally, in vivo experiments further validated the negative correlations between PRXL2A, oxidative stress, and osteoclast differentiation.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that enhanced oxidative stress in SIONFH patients reduces PRXL2A expression, which may promote osteoclast differentiation, thereby accelerating local femoral head bone destruction and contributing to SIONFH progression.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149676"},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662401","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":"Sex-biased microRNA expression in the developing mouse brain: Multiple mechanisms driving its origin","authors":"Susanna Szakats,&nbsp;Rachel Cannon,&nbsp;Megan J. Wilson","doi":"10.1016/j.gene.2025.149675","DOIUrl":"10.1016/j.gene.2025.149675","url":null,"abstract":"<div><div>The developing mouse brain exhibits sex-biased microRNA (miRNA) expression driven by complex genetic, regulatory, and hormonal mechanisms. This study explored six hypotheses contributing to sex-biased miRNA expression in the E15.5 mouse brain: Y-chromosome linkage, escape from X to inactivation, regulation by sex-biased transcription factors, co-regulation of sex-biased miRNAs with their host genes, interaction of biological sex and miRNA processing, and transcriptional regulation by the estrogen receptor (ER) pathway. Evidence supports all of the mechanisms tested, except Y-linkage, as contributors to sex-biased miRNA expression. The combination of genetic factors, regulatory mechanisms, and hormonal influences reinforces the notion that miRNA expression in the developing brain has evolved to drive sex-related differences. Understanding these mechanisms is crucial for elucidating the observed sex disparities in various aspects of neurodevelopment and etiology of neurodevelopmental disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149675"},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662402","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":"Mechanisms of matrix metalloproteinase 16 in development and cancer","authors":"Hao Cheng ,&nbsp;Mingjie Xu ,&nbsp;Jialai Zou,&nbsp;Lijian Xu","doi":"10.1016/j.gene.2025.149657","DOIUrl":"10.1016/j.gene.2025.149657","url":null,"abstract":"<div><div>Matrix metalloproteinases belong to a family of zinc ion-dependent protein hydrolases involved in extracellular matrix remodeling. As an important member of MMPs, MMP-16 plays a significant role in numerous biological processes and disease mechanisms within the organism. Its elevated expression levels are frequently observed in various malignant tumors, and this elevation is strongly related to tumor progression and patient outcomes. Therefore, many studies have been conducted to understand the mechanisms underlying MMP-16′s role in diseases. This paper mainly reviews the strict regulation of MMP-16′s expression and activity, and systematically elucidates its mechanism of action in growth, development, and cancer, showing the potential of MMP-16 as a therapeutic target in cancer, to provide new ideas and rationale for the development of novel antitumor drugs and cancer treatment protocols.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149657"},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657000","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}