Gene Reports最新文献

{"title":"An update on TWEAK/Fn14 signaling pathway: A comprehensive review","authors":"Ujjawal Sharma ,&nbsp;Arpit Mehrotra ,&nbsp;Bunty Sharma ,&nbsp;Abhilasha Sood ,&nbsp;Kartin Sak ,&nbsp;Shafiul Haque ,&nbsp;Nidarshana Chaturvedi Parashar ,&nbsp;Madhu Gupta ,&nbsp;Hardeep Singh Tuli","doi":"10.1016/j.genrep.2025.102403","DOIUrl":"10.1016/j.genrep.2025.102403","url":null,"abstract":"<div><div>Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional protein, present in various cell types and tissues, which, upon binding to the receptor factor-inducible 14 (Fn14), is involved in diverse pathologic processes including cell proliferation and death, angiogenesis, carcinogenesis, and inflammation. Interestingly, any alterations of their intracellular signaling are well correlated with the advancement of several diseases. The expression of TWEAK and Fn14 is augmented in many solid tumors compared with healthy tissues, thus leading to the enhancement of the proliferation, invasion, and subsequent migration of tumor cells. However, few TWEAK/Fn14 targeting pharmacological agents involved in inhibiting the progression of tumors have shown initial success in both clinical and pre-clinical experimental settings. Moreover, such agents improved angiogenesis, pro-inflammatory cytokine expression, and epithelial–mesenchymal transitions, upon TWEAK/Fn14 activation. This review provides an overview of the current understanding of the TWEAK–Fn14 signaling axis, its role in augmenting pathological characteristics of various diseases, and the existence of potential therapeutic targets for the development of novel pharmacological interventions.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102403"},"PeriodicalIF":0.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic basis of NMN and rapamycin in aging biology: Independent and intersecting pathways","authors":"C. Sasidhar ,&nbsp;V. Chitra ,&nbsp;V. Naveen Kumar","doi":"10.1016/j.genrep.2025.102401","DOIUrl":"10.1016/j.genrep.2025.102401","url":null,"abstract":"<div><div>Aging is a worldwide concern as populations are growing old, and there is increasing demand to find effective interventions capable of delaying the effects of age and thereby increasing healthspan. Nicotinamide mononucleotide (NMN) and rapamycin are two mechanistically different but potentially synergistic agents that target major hallmarks of aging, as part of emerging geroprotective. NMN is a precursor of NAD⁺, which activates sirtuins, maintains genomic stability, promotes mitochondrial activity; whereas rapamycin prevents activation of mTORC1 signaling through supporting autophagy and restricting cellular senescence and regulating immune response. This review has critically discussed the pharmacological molecular mechanism of NMN and rapamycin and their potential benefits in aging-associated pathways and preclinical and early clinical trials. We analyze the cross-communication between the NAD⁺/sirtuin and mTOR/autophagy axes, paying attention to the possibility of complementary regulation of the two systems to deliver synergistic effects against aging. Compared to other drugs that can be described as geroprotectors, including metformin, resveratrol, spermidine, and senolytics, NMN and rapamycin offer complementary mechanisms of action in a broader therapeutic context. To validate that this dual-pathway approach is safe and effective, we finally enumerate the challenges of translation dosing optimisation, biomarker development, and regulatory challenges. The association between NMN and rapamycin has shown a potential future in anti-aging medicine, as it has the potential to transform the paradigm of age-related disease therapy.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102401"},"PeriodicalIF":0.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From microbes to medicine: How microbiota profiling is shaping the future of cancer therapy","authors":"Anna Abdolshahi ,&nbsp;Ramtin Naderian ,&nbsp;Hamed Tahmasebi ,&nbsp;Elham Paraandavaji ,&nbsp;Mohammad Amin Hemmati ,&nbsp;Setayesh Kashanipoor ,&nbsp;Majid Eslami","doi":"10.1016/j.genrep.2025.102402","DOIUrl":"10.1016/j.genrep.2025.102402","url":null,"abstract":"<div><div>Microbiota profiling is increasingly recognized as fundamental in advancing personalized cancer therapy. Beyond identifying microbial biomarkers, this review positions microbiota profiling as a dynamic and functional axis in precision oncology capable of both informing patient stratification and being therapeutically modulated to enhance treatment efficacy. By uncovering the dynamics of host-microbiota interactions, it sheds light on their impact on carcinogenesis, tumor progression, and treatment outcomes. This review synthesizes the latest advancements, ongoing challenges, and future directions for microbiome-based strategies in cancer treatment. This study adopts a narrative review approach, synthesizing findings from peer-reviewed articles indexed in PubMed, Web of Science, and Scopus, using a focused search strategy, as detailed in the methodology. The focus centers on microbiota profiling, its roles in cancer therapy, and related therapeutic implications. Microbiota profiling facilitates detailed characterization of microbial ecosystems and their involvement in cancer development and treatment. The next-generation sequencing, metabolomics, and machine learning have enhanced the discovery of microbial biomarkers. Emerging microbiota-focused interventions, including fecal microbiota transplantation and probiotic therapies, show promise in improving responses to immunotherapy and chemotherapy. However, clinical implementation faces hurdles such as interindividual variability, lack of standardization, and ethical complexities. Microbiota profiling represents a revolution for personalizing cancer treatments. This review synthesizes recent advances in microbiome-focused analytical technologies and examines their implications for cancer diagnosis, treatment, and immune modulation, highlighting key translational opportunities and future directions in oncology.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102402"},"PeriodicalIF":0.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Wnt signaling-related gene expression and clinical features in Iranian colorectal cancer patients: A potential diagnostic insight","authors":"Mostafa Zargar ,&nbsp;Ahdieh Hosseini Anvari ,&nbsp;Mohammad Hadi Abbasian ,&nbsp;Amir Hossein Alipour ,&nbsp;Reza Shirkoohi ,&nbsp;Shahla Mohammad Ganji","doi":"10.1016/j.genrep.2025.102395","DOIUrl":"10.1016/j.genrep.2025.102395","url":null,"abstract":"<div><div>Aberrant activation of the Wnt signaling pathway plays a central oncogenic role in colorectal cancer (CRC). However, the expression profiles and clinical significance of multiple Wnt-related genes remain underexplored, particularly in specific populations such as Iranian patients. This study aimed to evaluate the expression of six key Wnt-associated genes and their associations with clinicopathological features in CRC tissues.</div><div>A case-control study was conducted using 40 advanced colorectal carcinoma tissues and 35 adjacent normal tissues obtained from Imam Khomeini Hospital, Tehran (2016–2017). Total RNA was extracted and reverse-transcribed, followed by quantitative real-time PCR. Gene expression levels were normalized to β-actin as the reference gene, and correlations with TNM staging parameters were analyzed statistically.</div><div>Five genes (HIF-1α, GSK3β, BCL9, CCND1, CDK1) were significantly upregulated in CRC tissues compared to normal controls (all <em>P</em> &lt; 0.05), whereas MLH1 was downregulated (<em>P</em> = 0.052, borderline significance). MLH1 expression showed significant negative correlations with tumor stage, lymph node involvement (N), and metastasis (M) (all <em>P</em> = 0.02). GSK3β expression correlated with metastatic status (<em>P</em> = 0.002), BCL9 with tumor size (T) and nodal involvement (<em>P</em> &lt; 0.05), and HIF-1α with tumor stage and nodal status (P &lt; 0.05).</div><div>This multi-gene expression analysis reveals coordinated dysregulation of Wnt pathway components in CRC, with distinct correlation patterns linking specific genes to disease progression markers. These findings suggest potential applications in molecular staging and therapeutic targeting for Iranian CRC patients.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102395"},"PeriodicalIF":0.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caloric restriction modulates liver transcriptomes in an age-dependent manner in C57BL/6 N mice","authors":"Lisha Wei ,&nbsp;Yikai Huang ,&nbsp;Junyi Zheng ,&nbsp;Xuemin Xu ,&nbsp;Jian Hong ,&nbsp;Dehui Sun ,&nbsp;Yanyan Zheng ,&nbsp;Xiuke Ouyang","doi":"10.1016/j.genrep.2025.102398","DOIUrl":"10.1016/j.genrep.2025.102398","url":null,"abstract":"<div><div>Caloric restriction (CR) is a well-established dietary intervention that promotes longevity and metabolic health; however, its age-dependent transcriptional effects on the liver remain unclear. Here, we aimed to delineate how CR remodels the hepatic transcriptome across 4, 9, 13, and 18 months of age in male C57BL/6 N mice and to determine whether the transcriptional response to CR is progressively attenuated in old age. We performed RNA sequencing on liver tissues from mice maintained on control or CR diets at 4, 9, 13, and 18 months of age to characterize transcriptional remodeling across aging.</div><div>Age was the primary determinant of global expression variance, whereas CR induced distinct, age-specific gene expression changes. The strongest responses occurred at 9 and 13 months, where CR upregulated genes related to circadian regulation, fatty acid metabolism, DNA replication, and repair, while suppressing inflammatory and lipogenic pathways. By 18 months, CR effects were attenuated, although circadian and metabolic signatures remained evident.</div><div>Functional enrichment analyses revealed consistent activation of PPARα-associated lipid metabolism, bile acid homeostasis, and circadian rhythm pathways, accompanied by repression of type I interferon-mediated immune signaling. Together, these findings show that CR elicits dynamic, age-dependent transcriptional reprogramming in the liver, enhancing metabolic and genomic maintenance programs in midlife (9–13 months) and dampening inflammatory responses, with reduced plasticity observed at 18 months. These findings suggest that CR exerts its strong and most multifaceted effects on hepatic metabolic and immune pathways in midlife, but that these transcriptional benefits become substantially blunted in old age, highlighting the importance of the timing of dietary interventions during the aging process.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102398"},"PeriodicalIF":0.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PGK1 is a prognostic molecule and silencing PGK1 inhibits the growth in breast cancer cells","authors":"Zhenzhen Yang ,&nbsp;Ying Han","doi":"10.1016/j.genrep.2025.102396","DOIUrl":"10.1016/j.genrep.2025.102396","url":null,"abstract":"<div><h3>Background</h3><div>Due to its persistently high prevalence and mortality, breast cancer (BC) remains a significant public health challenge. The present study comprehensively investigates the role of PGK1 (Phosphoglycerate Kinase 1) in BC, recognizing its critical involvement in tumorigenesis and disease progression despite the scarcity of reports addressing its specific implications.</div></div><div><h3>Methods</h3><div>Genomic microarray datasets and associated clinicopathological records were acquired from two publicly accessible repositories: the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Comprehensive comparative investigations were conducted, covering functional enrichment evaluation, characterization of the tumor immune microenvironment, and assessment of pharmacological responsiveness in BC. Experimental validation of PGK1's biological functions in BC was further carried out using both in vitro experimental models and in vivo animal systems. Statistical processing and graphical representations of data were primarily executed using the R programming environment.</div></div><div><h3>Results</h3><div>Experimental results revealed a marked elevation in PGK1 expression levels within BC tissues, correlating with unfavorable clinical outcomes. Clinical association studies identified substantial relationships between PGK1 abundance and critical pathological markers in BC, such as estrogen receptor (ER) positivity, progesterone receptor (PR) status, and human epidermal growth factor receptor 2 (Her-2) expression levels. Gene Set Enrichment Analysis (GSEA) demonstrated PGK1's prominent engagement in fundamental cellular mechanisms, particularly mitotic regulation and genomic replication processes. Additionally, systematic evaluation revealed significant co-variation patterns between PGK1 and immune checkpoint regulators. Pharmacogenomic assessments established proportional relationships between PGK1 expression and therapeutic responses to specific agents, including AT-7519, Methotrexate, and MS-275. In cell experiments, silencing PGK1 resulted in a marked decrease in cellular proliferation and migration abilities, accompanied by an increase in apoptosis levels. In nude mouse tumorigenesis experiments, PGK1 knockdown significantly slowed tumor growth. Overall, both in vitro and in vivo results demonstrate that reduced PGK1 expression markedly affects BC cell growth.</div></div><div><h3>Conclusions</h3><div>This study systematically validates PGK1's prognostic value, clinical associations, and functional relevance in BC, while integrating multi-omics data (transcriptomic, clinical, immune, and pharmacogenomic) to clarify its subtype-specific roles. The findings might position PGK1 as a high-priority therapeutic candidate for targeted intervention strategies against breast malignancies.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102396"},"PeriodicalIF":0.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of BRCA1/BRCA2 pathogenic variants implicated in prostate cancer by next-generation sequencing","authors":"Khaoula Elghazali ,&nbsp;Youssef Ennaji ,&nbsp;Abdelilah Laraqui ,&nbsp;Ahmed Ameur ,&nbsp;Moulay Mustapha Ennaji","doi":"10.1016/j.genrep.2025.102397","DOIUrl":"10.1016/j.genrep.2025.102397","url":null,"abstract":"<div><div>Prostate cancer poses a significant public health challenge worldwide, and its hereditary forms are increasingly recognized in clinical practice. Pathogenic variants in the BRCA1 and BRCA2 genes contribute to the risk of hereditary prostate cancer, but data from North African populations are still limited. This study examined germline variants in the BRCA1/2 genes in 30 Moroccan patients diagnosed with prostate cancer. Next-generation sequencing was used to analyze the full coding regions and intron-exon boundaries of both genes.</div><div>Two deleterious frameshift insertions were identified: BRCA1 c.3514_3515insT and BRCA2 c.4240_4241insA, each detected in two unrelated patients. These gene carriers had high-risk disease (tumor stage ≥ 2 and Gleason score ≥ 7). A BRCA2 variant of uncertain significance (c.681 + 56C &gt; T) was present in almost half of the cohort, alongside several intronic variants and benign polymorphisms. Importantly, almost half of the identified variants were absent from existing North African genomic databases.</div><div>These findings provide new insights into the spectrum of BRCA1/2 germline variants in prostate cancer and highlight the need for reference genomic data on ancestry. Broader inclusion of underrepresented populations will be essential to improve variant interpretation and guide precision medicine in hereditary prostate cancer worldwide.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102397"},"PeriodicalIF":0.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational exploration of novel (p.L328P) and reported (p.R209Q) variants identified in Glial Fibrillary Acidic Protein (GFAP) gene in a patient with Alexander disease from India","authors":"Surajit Malakar ,&nbsp;Tathagata Das ,&nbsp;Tamali Halder ,&nbsp;Vikrant Yadav ,&nbsp;Anurag Sahu ,&nbsp;Parimal Das","doi":"10.1016/j.genrep.2025.102393","DOIUrl":"10.1016/j.genrep.2025.102393","url":null,"abstract":"<div><h3>Background</h3><div>Alexander disease (AxD) is a rare, progressive and fatal neurological disorder characterized by degeneration of the white matter of the brain accompanied by the formation of Rosenthal fibers, distinct cytoplasmic inclusion within astrocytes (non-neuronal cells) in the brain. The disease phenotype is commonly identified to be associated with heterozygous <em>de novo</em> variation in the Glial Fibrillary Acidic Protein (<em>GFAP</em>) gene. Rare instances of familial AxD have also been reported with genetic anticipation.</div></div><div><h3>Methods and result</h3><div>The study aimed to determine the genetic cause of a clinically diagnosed case of juvenile AxD from India with macrocephaly and psychomotor delay, followed by regression, spastic paraparesis, and feeding difficulties. DNA was extracted from peripheral blood sample and was taken for whole-exome-sequencing. Two pathogenic heterozygous missense variations were identified in <em>GFAP,</em> the potential candidate for AxD (c.626G &gt; A leading to p.R209Q and c.983 T &gt; C leading to p.L328P), notably, p.L328P is being reported here first time. The karyotype of the proband revealed no chromosomal anomalies. Following confirmation by Sanger sequencing, variants including their cumulative effect in Double Mutant were characterized <em>in silico</em> for prediction of pathogenicity, protein stability, physiochemical analysis, molecular simulation, principal component analysis and molecular docking. Collectively, these findings reveal both compensatory and synergistic effects that may influence intermediate filament dynamics and related signaling pathways.</div></div><div><h3>Conclusion</h3><div>This altered GFAP protein gets accumulated in the cytoplasm of the astrocyte cells, leading to the formation of Rosenthal fibers, which impairs cell function. While <em>in silico</em> analysis supports the pathogenic nature of the studied variants, which is consistent with the observed AxD pathophysiology in the current study.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102393"},"PeriodicalIF":0.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction in peripheral expression of the TMLHE gene in Turkish youth with autism spectrum disorder","authors":"İpek Kuşcu Özücer ,&nbsp;Alper Alnak ,&nbsp;Hilal Akköprü ,&nbsp;Zeynep Nur Karadoğan ,&nbsp;Ahmet Okay Çağlayan ,&nbsp;Saliha B. Selman ,&nbsp;Murat Coskun","doi":"10.1016/j.genrep.2025.102391","DOIUrl":"10.1016/j.genrep.2025.102391","url":null,"abstract":"<div><h3>Background</h3><div>Trimethyllysine Hydroxylase, Epsilon (<em>TMLHE</em>) gene mutations have been clinically associated with an increased risk of autism spectrum disorder (ASD). This study aimed to evaluate the peripheral expression profile of the <em>TMLHE</em> gene and its association with ASD phenotype in a clinical sample of youth diagnosed with ASD.</div></div><div><h3>Methods</h3><div>The study sample included 205 participants (ASD: <em>n</em> = 100; controls: <em>n</em> = 105, <em>M</em>_<em>age</em> = 9.25 years, <em>SD</em> = 3.74). The Childhood Autism Rating Scale and the Aberrant Behavior Checklist were administered to assess the severity of ASD and associated symptoms. Peripheral blood samples were collected from all participants, and <em>TMLHE</em> gene expression levels were analyzed using quantitative reverse transcription PCR (RT-qPCR).</div></div><div><h3>Results</h3><div><em>TMLHE</em> gene expression was significantly downregulated in the ASD group compared to controls (<em>p</em> &lt; .001). Notably, significant correlations were identified between <em>TMLHE</em> expression levels and the CARS subscales for object use (<em>p</em> = .043) and listening response (<em>p</em> = .038).</div></div><div><h3>Conclusion</h3><div>This study represents the first case-control investigation of peripheral <em>TMLHE</em> gene expression in ASD, revealing that <em>TMLHE</em> expression is reduced in children with ASD compared to typically developing peers. These findings contribute to a deeper understanding of the potential implications of <em>TMLHE</em> gene mutations in the etiology of ASD.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102391"},"PeriodicalIF":0.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of epigenetic alterations induced by genistein, EGCG, luteolin, and hesperidin in breast cancer: A systematic review","authors":"Amirhossein Rajabalinejad ,&nbsp;Mahsa Jalili ,&nbsp;Rasool Rajabi ,&nbsp;Maryam Nazari","doi":"10.1016/j.genrep.2025.102394","DOIUrl":"10.1016/j.genrep.2025.102394","url":null,"abstract":"<div><div>Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA regulation, have attracted attention as potential cancer therapy targets. Breast cancer is heavily influenced by epigenetic dysregulation (<em>e.g.</em>, BRCA1/2 tumor suppressor genes deactivation) alongside genetic and environmental factors. Dietary flavonoids in fruits and vegetables, such as genistein, epigallocatechin gallate, luteolin, and hesperidin, have been shown to regulate epigenetic pathways by reversing these aberrations. The motive of this systematic review is to evaluate studies reporting flavonoid-induced epigenetic changes in breast cancer and their potential to overcome therapy resistance. A systematic search was conducted across PubMed, Scopus, Web of Science, and Cochrane from inception to February 2025, identifying 550 studies. Studies were selected based on their focus on selected flavonoids, use of <em>in vivo</em> or <em>in vitro</em> experiments, and breast cancer models. Ultimately, 48 eligible studies were included for qualitative synthesis, in which genistein (24 studies) and EGCG (19 studies) were the most extensively investigated; these compounds demonstrated consistent demethylation effects and regulation of histone and microRNA expression, whereas luteolin (7 studies) and hesperidin (2 studies) showed preliminary yet promising outcomes. Most of the studies show robust preclinical data with low bias (45/48 studies) across diverse models; however, there are bioavailability challenges and limited studies on epigenetic effects of hesperidin and luteolin. The chemopreventive role and synergistic potentials with conventional agents support flavonoids as potential complementary therapies for breast cancer, though further clinical validation and strategies for bioavailability optimization are merited.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102394"},"PeriodicalIF":0.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}