Genes & genomics最新文献

{"title":"Transcriptomic analysis reveals functional compartmentalization of the digestive tract in Urechis unicinctus.","authors":"Kyoung-Bin Ryu, Geon Woo Lee, Chan-Jun Lee, Min-Ji Song, Sung-Jin Cho","doi":"10.1007/s13258-026-01767-7","DOIUrl":"10.1007/s13258-026-01767-7","url":null,"abstract":"","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"987-995"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining ocular safety assessment: retinal organoids as platforms for predicting human ocular toxicology.","authors":"Yung Hyun Choi, Sun-Hee Leem","doi":"10.1007/s13258-026-01778-4","DOIUrl":"10.1007/s13258-026-01778-4","url":null,"abstract":"<p><p>Despite the substantial progress in drug discovery and precision therapeutics, the predictive power of current ocular safety assessments remains limited owing to the lack of human experimental models. Conventional two-dimensional cell cultures lack the complex laminar organization, multicellular interactions, and functional electrophysiological properties of the human retina. Additionally, animal models frequently exhibit species-specific differences in retinal development, metabolism, and stress responses that hinder translational accuracy. Human induced pluripotent stem cell-derived retinal organoids are transformative microphysiological platforms that recapitulate key aspects of the human retinal architecture, including photoreceptor differentiation, synaptic connectivity, and neuronal functionality within a three-dimensional and human-derived context. In addition to structural resemblance, these systems enable multidimensional and mechanism-related toxicity assessments of oxidative stress, mitochondrial dysfunction, lysosomal impairment, ferroptotic signaling, synaptic dysregulation, and adaptive cytoprotective pathways. Therefore, retinal organoids can be incorporated into quantitative and regulatory toxicological frameworks using concentration-response modeling, benchmark dose derivation, and adverse outcome pathway mapping. Notably, these models identify the reactive oxygen species-mitochondria-lysosome axis as a central vulnerability hub that mechanistically links diverse exposure modalities, including small-molecule drugs, biologics, gene therapies, and nanomaterials, to photoreceptor degeneration. Ongoing advances in maturation, vascular-like integration, microfluidic coupling, and interline reproducibility have further enhanced their translational value. Collectively, retinal organoids are redefining ocular safety assessments by shifting the paradigm from hazard identification to predictive, mechanism-based, and human toxicology.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"951-962"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded SSR profile database for forensic discrimination and phylogenetic analysis in cultivars of spring orchid (Cymbidium goeringii).","authors":"Kyung Suk Lee, Yu Bin Kim, Juha Kim, Sam-Geun Kong, Ki Wha Chung","doi":"10.1007/s13258-026-01776-6","DOIUrl":"10.1007/s13258-026-01776-6","url":null,"abstract":"<p><strong>Background: </strong>Cymbidium goeringii is one of the most widely cultivated and traded ornamental orchids in East Asia. Due to its high horticultural value and phenotypic variability, accurate cultivar identification is essential but challenging, as their flowers bloom only briefly in spring.</p><p><strong>Objective: </strong>We have developed a forensic tool for rapid and exact cultivar discrimination by applying 12 simple sequence repeat (SSR) profiles in C. goeringii. This study was performed to establish an expanded SSR dataset for cultivar identification and phylogenetics in C. goeringii.</p><p><strong>Methods: </strong>We examined a total of 6,051 samples from 269 cultivars, including 92 Korean cultivars with ≥ 10 samples each. Among these, representative combined genotypes (CG1) were determined, and their frequencies (CG1%) were used to assess genetic concordance among samples. Phylogenetic trees were constructed using both Euclidean and codominant genetic distances, and cultivar distributions were visualized using Principal Coordinate Analysis (PCoA) and t-SNE.</p><p><strong>Results: </strong>Approximately 72.8% of the samples matched their dominant combined genotype (CG1), suggesting that nearly 30% of cultivated orchids may exhibit genotype discordance. Phylogenetics and PCoA showed a weak or no correlation between phenotypes, while they revealed relatively clear clustering between Korean and Japanese origins.</p><p><strong>Conclusion: </strong>These results highlight the value of integrating multiple analytical methods to enhance interpretability. The expanded SSR genotype dataset presented here offers a robust resource for cultivar identification, verifying genotype concordance, phylogenetic analysis, and ecological genetics research. This study will be an important milestone in the forensic application of plants with diverse cultivars exhibiting a wide range of horticultural and commercial values.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1029-1043"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory activity and antioxidant capacity of Clerodendrum japonicum (Thunb.) sweet extract in LPS-stimulated macrophages.","authors":"Jeongeun Noh, Kyeoungtae Park, Fred Pitisopa, Myknee Qusa Sirikolo, Jung Jin Kim, Sung-Suk Suh, Jong Bae Seo","doi":"10.1007/s13258-026-01769-5","DOIUrl":"10.1007/s13258-026-01769-5","url":null,"abstract":"<p><strong>Background: </strong>Clerodendrum japonicum (Thunb.) Sweet is a medicinal plant native to East Asia, including Korea, Japan, and China. Its leaves have traditionally been used to relieve respiratory symptoms and inflammatory conditions. However, no studies have systematically explored its anti-inflammatory activity and antioxidant capacity.</p><p><strong>Objective: </strong>This study aimed to investigate the anti-inflammatory effects of C. japonicum (Thunb.) Sweet extract (CJSE) in a lipopolysaccharide (LPS)-induced inflammatory model and determine its antioxidant capacity.</p><p><strong>Methods: </strong>Anti-inflammatory activity was investigated in LPS-stimulated RAW 264.7 macrophages by evaluating nitric oxide (NO) production, inflammatory gene expression, and related signaling pathways. Antioxidant capacity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and by determining total phenolic and flavonoid contents.</p><p><strong>Results: </strong>CJSE reduced LPS-induced NO production in a dose-dependent manner without detectable cytotoxicity. CJSE also decreased the expression of key inflammatory mediators, including inducible nitric oxide synthase and cyclooxygenase-2, and proinflammatory cytokine genes, such as tumor necrosis factor-α, interleukin-6, and interferon-β. Mechanistically, CJSE was associated with reduced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) in LPS-stimulated cells. Moreover, CJSE demonstrated strong DPPH and ABTS radical scavenging activities and contained substantial levels of phenolic and flavonoid compounds, which supported its antioxidant potential.</p><p><strong>Conclusion: </strong>CJSE suppresses LPS-induced inflammatory responses in macrophages and exhibits remarkable antioxidant capacity, suggesting that it could serve as a potential natural source of bioactive compounds for managing inflammation and oxidative stress.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"997-1006"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomic analysis reveals KRAS-associated gene activation and epigenetic regulation in mutant IDH1 glioma.","authors":"Jinha Jeon, Jiyoon Park, Sujeong Gim, Chan Chung","doi":"10.1007/s13258-026-01775-7","DOIUrl":"10.1007/s13258-026-01775-7","url":null,"abstract":"<p><strong>Background: </strong>Mutations in isocitrate dehydrogenase 1 (IDH1) are hallmark features of diffuse gliomas and drive extensive metabolic and epigenetic reprogramming through accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). However, the downstream transcriptional programs and chromatin-based mechanisms linking mutant IDH1 to oncogenic signaling remain incompletely understood.</p><p><strong>Objective: </strong>This study aimed to define transcriptional changes associated with the IDH1 R132H mutation and to determine how epigenetic mechanisms influence KRAS-associated gene expression.</p><p><strong>Methods: </strong>We analyzed transcriptomic data from the TCGA-LGG cohort and public RNA-seq datasets to identify differentially expressed genes and enriched pathways. Key findings were validated using qRT-PCR in cellular models expressing IDH1 R132H. To assess epigenetic regulation, we performed knockdown experiments targeting the H3K36 methyltransferases SETD2 and SMYD5.</p><p><strong>Results: </strong>Integrated transcriptomic analyses revealed consistent enrichment of KRAS signaling-related gene signatures in IDH1 R132H tumors and cell models. qRT-PCR validation confirmed altered expression of key KRAS-associated genes involved in immune response, extracellular matrix remodeling, and tumor-related processes. Notably, the knockdown of SETD2 or SMYD5 significantly reduced the expression of these genes, indicating that H3K36 methylation-associated chromatin regulation contributes to their transcriptional activation.</p><p><strong>Conclusion: </strong>These findings demonstrate that mutant IDH1 promotes KRAS-associated transcriptional programs, at least in part, through epigenetic mechanisms involving H3K36 methylation-dependent chromatin regulation in glioma.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1017-1027"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics and machine learning identify RNF144B and C5AR1 as immune-related molecular signatures and therapeutic targets in myocardial infarction.","authors":"Yuxin Hu, Lu Chen, Jianmei Sha, Caihong Shao, Junli Gao, Jianhua Yao","doi":"10.1007/s13258-026-01753-z","DOIUrl":"10.1007/s13258-026-01753-z","url":null,"abstract":"<p><p>BACKGROUND: Myocardial infarction (MI) is a life-threatening cardiovascular disease characterized by high morbidity and mortality. Although advances in clinical management have improved patient outcomes, early diagnosis and effective immunomodulatory therapies remain limited. OBJECTIVE: This paper aims to identify key regulatory genes in MI, uncover their underlying mechanisms of action of the key genes, and facilitate their diagnostic and therapeutic use. METHODS: In this study, we integrated multiple transcriptomic datasets and applied machine learning approaches, including LASSO regression, to identify a robust 13 key genes significantly associated with MI. GSEA and GSVA were subsequently performed to explore their potential biological functions. The immunological relevance of these genes was evaluated by analyzing their correlations with inflammation-related genes and those involved in immune cell migration. In addition, transcription factor and microRNA (miRNA) regulatory networks were constructed to elucidate upstream regulatory mechanisms. The expression levels of the 13 key genes were validated in MI mouse model. RESULTS: Among 11 cardiac cell populations identified, myeloid cells contributed most prominently to MI pathogenesis. A robust 13-gene predictive signature was established, with RNF144B and C5AR1 showing strong associations with immune modulation and disease severity. Correlation analysis demonstrated a significant positive relationship of RNF144B and C5AR1 with immunological roles. TF-gene and miRNA–mRNA regulatory networks supported the post-transcriptional regulation of these genes. In the MI mouse model, expression of the 13 genes was consistent with the risk-prediction model. Molecular docking identified CCX168 as a promising small-molecule candidate targeting RNF144B and C5AR1. CONCLUSION: This study identified 13-gene signature, particularly RNF144B and C5AR1, holds promise as therapeutic targets, providing new insights for immunomodulatory and precision medicine strategies in MI.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"847-865"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis of zonula occludens-1 (ZO-1) knockout in ovarian cancer cell lines.","authors":"Hyojin An, Heungyeol Kim, Do-Ye Kim, Hyung Joon Yoon, Ji Young Lee, Wan Kyu Eo, Min Young Kim, Ki Hyung Kim, Hee-Jae Cha","doi":"10.1007/s13258-026-01761-z","DOIUrl":"10.1007/s13258-026-01761-z","url":null,"abstract":"<p><strong>Background: </strong>Zonula occludens-1 (ZO-1) is a crucial tight junction protein that regulates intercellular permeability and adhesion, thereby preserving the integrity of epithelial and endothelial barriers. ZO-1 is associated with tumorigenesis and the progression of epithelial-mesenchymal transition (EMT), invasion, and metastasis. In our previous study, knockout (KO) of ZO-1 using clustered regularly interspaced short palindromic repeats (CRISPR) reduced proliferation but increased migration and invasion, suggesting that ZO-1 may have a dual role. Therefore, this study aimed to elucidate the role of ZO-1 in ovarian cancer by analyzing transcriptomic changes associated with ZO-1.</p><p><strong>Objective: </strong>This study aims to elucidate the impact of ZO-1 KO on gene expression in ovarian cancer cells by performing comparative RNA sequencing (RNA-seq) analysis on two distinct ZO-1 KO ovarian cancer cell lines, SKOV3 and SNU119.</p><p><strong>Methods: </strong>ZO-1 was knocked out in SKOV3 and SNU119 cells using CRISPR-Cas9 technology. After identifying differentially expressed genes (DEGs) through RNA sequencing, Gene Ontology (GO) and pathway enrichment analyses were performed. The selected targets were subsequently validated using reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis to assess both transcript- and protein-level expression changes.</p><p><strong>Results: </strong>Transcriptomic analysis revealed over 400 DEGs in each cell line. Of these, 14 genes were consistently upregulated in both cell lines, while 24 genes were consistently downregulated. The common DEGs were visualized using a heatmap, and a subset of these genes was further validated by RT-qPCR and Western blot analyses. TGFB2 expression was consistently altered at both the mRNA and protein levels following ZO-1 KO in both cell lines. Similar expression patterns were observed for THBS1, VCAN, ITGB8, SEMA3A, and GAS6. The concordant changes observed in transcriptomic and protein analyses suggest a consistent association between ZO-1 KO and TGFB2 expression.</p><p><strong>Conclusion: </strong>ZO-1 KO in ovarian cancer cells induces substantial transcriptional reprogramming, particularly affecting genes associated with extracellular matrix organization and signaling pathways. Multiple candidate genes showed consistent alterations at both the mRNA and protein levels, supporting the robustness of the observed transcriptional changes. These findings provide a framework for understanding ZO-1-associated regulatory networks in ovarian cancer.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"911-921"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEMA4A promotes acute myeloid leukemia progression through inhibiting apoptosis.","authors":"Xinyu Li, Binyu Yao, Meiling Sun, Wangshi Li, Xingzhi Lv, Keyang Luo, Yue Wu, Ruolin Xiu, Yuzhu Ma, Fukai Liu, Yanhong Zhao, Shengjin Fan, Linqing Tang, Huitao Fan","doi":"10.1007/s13258-026-01763-x","DOIUrl":"10.1007/s13258-026-01763-x","url":null,"abstract":"<p><p>BACKGROUND: Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy. Currently, targeted therapy represents a transformative approach in the treatment of this disease. Semaphorin 4A (SEMA4A) is a member of the semaphorin family of soluble and transmembrane proteins. Recent evidence further identifies it as a novel immunotherapeutic target in myeloma. However, its functional significance in AML remains elusive. OBJECTIVE: This study investigates the expression of SEMA4A in AML and its potential pathogenic mechanisms. METHODS: Initially, we performed database analysis to evaluate SEMA4A expression. To investigate its biological function, SEMA4A was silenced in AML cells via shRNA, and RT-qPCR and Western blot confirmed its knockdown. Apoptosis, differentiation, and cell cycle were assessed by flow cytometry. Combination drug assays further validated a role of SEMA4A in mediating chemoresistance. In vivo, the growth of leukemic cells and mouse survival were assessed through xenotransplantation models. RNA sequencing ultimately uncovered the underlying mechanisms driving these phenotypes. RESULTS: SEMA4A deletion in AML cells reduced proliferative and clonogenic capacity. We observed increased apoptosis, enhanced differentiation, and G0/G1 cell cycle arrest. Furthermore, SEMA4A deletion in vivo prolonged survival. Mechanistically, RNA-seq analysis revealed significant activation of apoptotic pathways following SEMA4A loss. Notably, SEMA4A knockdown led to a marked reduction in BCL-2 expression and upregulation of the BCL-2 family members BMF and BBC3. SEMA4A deficiency also sensitized AML cells to chemotherapy, lowering effective drug doses and inducing extensive apoptosis. CONCLUSION: Our findings revealed the oncogenic role for SEMA4A, suggesting it represents a promising therapeutic target in AML patients. </p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"935-949"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDK9 inhibition triggers MT2A-dependent apoptosis in HCC cells.","authors":"Bilu Peng, Yuli Bao, Ziren Zhang, Jianxin Lyu, Linyong Du, Lei Zhang, Weifeng Ma","doi":"10.1007/s13258-025-01700-4","DOIUrl":"10.1007/s13258-025-01700-4","url":null,"abstract":"<p><p>BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. While cyclin-dependent kinase 9 (CDK9) is recognized as a crucial transcriptional regulator in cancer progression, its specific role in HCC pathogenesis remains poorly understood. OBJECTIVE: This study aims to investigate the specific role and underlying mechanisms of cyclin-dependent kinase 9 (CDK9) in the pathogenesis and progression of hepatocellular carcinoma (HCC). METHODS: CDK9 expression in HCC was analyzed through public databases and validated by immunohistochemistry (IHC) of clinical specimens. Compound 45 (CDK9 inhibitor) was used to assess CDK9’s functional impact. Mechanistic studies employed RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP), immunoblotting, RT-qPCR, flow cytometry, and colony formation assays. Antitumor efficacy was evaluated in xenograft models. RESULTS: Our study demonstrates significant CDK9 overexpression in HCC clinical samples, as confirmed through the cBioPortal for Cancer Genomics database analysis and IHC validation, with elevated expression correlating strongly with poor patient prognosis. Importantly, we reveal that pharmacological inhibition of CDK9 using Compound 45 potently induces apoptosis in HCC cells through a novel molecular mechanism. Mechanistic investigations show that CDK9 inhibition promotes c-Jun-mediated transcriptional activation of MT2A, leading to subsequent downregulation of the anti-apoptotic proteins BCL-2 and BCL-XL. Genetic ablation experiments confirm the essential role of MT2A in mediating this apoptotic pathway. Furthermore, in vivo studies using an HCC xenograft model demonstrate the significant tumor-suppressive effects of Compound 45 treatment. CONCLUSION: These findings collectively identify the CDK9/c-Jun/MT2A/BCL-2/BCL-XL axis as a critical therapeutic pathway in HCC, establishing CDK9 inhibition as a promising strategy for HCC treatment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"817-829"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF468 stabilization by RNF4 enhances apoptosis resistance and carboplatin resistance in breast cancer via transcription activation of XIAP.","authors":"Juan Hu, Guo Tian, Peizhi Tang, Sheng Yuan, Bingjian Jiang","doi":"10.1007/s13258-026-01760-0","DOIUrl":"10.1007/s13258-026-01760-0","url":null,"abstract":"<p><strong>Background: </strong>Carboplatin is a commonly utilized chemotherapy agent for breast cancer treatment, yet resistance to this drug remains a significant clinical challenge OBJECTIVE: The objective of this study was to investigate the role and regulatory mechanism of zinc finger protein 468 (ZNF468) in carboplatin resistance in breast cancer.</p><p><strong>Methods: </strong>To establish carboplatin-resistant cells, SK-BR-3 and MDA-MB-231 cells were exposed to increasing concentrations of carboplatin. ZNF468 expression was analyzed in clinical samples (carboplatin-resistant vs. sensitive patients, n=40) and carboplatin-resistant cells. Functional assays, including Cell Counting Kit-8 (CCK-8), EDU staining, flow cytometry, and colony formation assays, were conducted to evaluate cell viability and apoptosis. The interactions and underlying mechanisms were further explored using Chromatin immunoprecipitation (ChIP), luciferase reporter assays, co-immunoprecipitation (Co-IP), and cycloheximide chase assays.</p><p><strong>Results: </strong>ZNF468 was significantly elevated in carboplatin-resistant cells and tissues. Knockdown of ZNF468 reduced the growth of cells and increased apoptosis in drug-resistant cells. ZNF468 was found to transcriptionally activate X-linked inhibitor of apoptosis protein (XIAP), which contributed to enhanced resistance to apoptosis and carboplatin. In addition, RING Finger Protein 4 (RNF4) was shown to stabilize ZNF468 by promoting its phosphorylation, and this stabilization further aggravated the resistance to apoptosis and carboplatin treatment in breast cancer cells.</p><p><strong>Conclusion: </strong>RNF4 stabilized ZNF468, which transcriptionally activates XIAP, enhancing resistance to apoptosis and promoting carboplatin resistance in breast cancer. This study highlights the critical role of ZNF468 in carboplatin resistance, providing potential therapeutic targets for overcoming drug resistance in breast cancer treatment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"895-909"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}