Genes & genomics最新文献

{"title":"NGS-based identification of a MYO7A mutation in a Korean family with DFNB2, a subtype of autosomal recessive non-syndromic hearing loss.","authors":"Ye-Ri Kim, Byeonghyeon Lee, Hong-Joon Park, Tae-Jun Kwon, Un-Kyung Kim","doi":"10.1007/s13258-025-01653-8","DOIUrl":"https://doi.org/10.1007/s13258-025-01653-8","url":null,"abstract":"<p><strong>Background: </strong>Hereditary hearing loss (HHL) exhibits considerable genetic heterogeneity. Among the known causative genes, MYO7A is frequently linked to autosomal recessive non-syndromic hearing loss (ARNSHL), contributing to auditory dysfunction through impaired inner ear cellular mechanics.</p><p><strong>Objective: </strong>This study aimed to identify the genetic cause of ARNSHL in a Korean family (SR-323) and to assess the pathogenicity of candidate MYO7A variants.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed on five family members (two affected individuals and three unaffected relatives). Variant filtering, co-segregation analysis, and Sanger sequencing validation were conducted to identify candidate mutations. Conservation analysis across vertebrate species and in silico pathogenicity predictions were used to evaluate the biological impact of the variants. Additionally, 100 unrelated normal-hearing Korean individuals were screened to determine the frequency of the variant in the general population.</p><p><strong>Results: </strong>Two MYO7A variants, c.4501G > A (p.Val1501Met) and c.6070 C > T (p.Arg2024Stop), were identified in affected individuals in a compound heterozygous state. Unaffected family members carried only one heterozygous variant. Both amino acid residues were highly conserved across seven vertebrate species. In silico analyses predicted p.Val1501Met to be pathogenic, while c.6070 C > T was previously classified as likely pathogenic. These variants were absent in the normal-hearing cohort, and only individuals with both variants exhibited hearing loss, supporting a compound heterozygous inheritance.</p><p><strong>Conclusion: </strong>Compound heterozygosity of the MYO7A variants c.4501G > A and c.6070 C > T likely underlies the ARNSHL phenotype in the SR-323 family. These findings expand the known mutational spectrum of MYO7A and highlight the importance of genetic screening in hereditary hearing loss within the Korean population.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495841","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":"Foxj3 represses TGF-β signals-responsive transcriptions in Xenopus early development.","authors":"Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi","doi":"10.1007/s13258-025-01654-7","DOIUrl":"https://doi.org/10.1007/s13258-025-01654-7","url":null,"abstract":"<p><strong>Background: </strong>Forkhead box (Fox) proteins belong to a large family of transcription factors characterized by a highly conserved DNA binding domain termed the 'forkhead box'. They are involved in critical functions during early development and in the adult.</p><p><strong>Objective: </strong>In this work, Foxj3 was found to regulate negatively the transcription of target genes induced by Activin/Nodal or BMP signal in Xenopus embryos. Thus, we sought to investigate the molecular mechanisms underlying this function of Foxj3 as a transcriptional repressor.</p><p><strong>Methods: </strong>Microinjection of mRNA and anti-sense morpholino oligo was employed to achieve the gain- and loss-of Foxj3 function, respectively. RT-PCR and luciferase assays were performed to investigate the effects of overexpression or knockdown of Foxj3 on TGF-β signals-responsive transcriptions. Animal cap elongation assay was used to check whether Foxj3 would affect the dorsalization of ectodermal tissues induced by Activin signal. Whole-mount in situ hybridization was carried out to analyze the in vivo expression of key marker genes in the embryos overexpressing or depleted of Foxj3.</p><p><strong>Results: </strong>Overexpression of Foxj3 was found to repress the gene responses activated by Activin/Nodal or BMP4 signals. Its increased levels also caused defective mesodermal and ectodermal specification in embryo. Conversely, knockdown of Foxj3 augmented Nodal-responsive transcription of target genes. In line with this, Foxj3 morphants displayed the malformed phenotypes resembling those of embryos exposed to increased levels of Nodal signal. Furthermore, Foxj3 repression of transcriptional responses was blocked by depletion of RNF152 or co-expression of β-catenin.</p><p><strong>Conclusion: </strong>Foxj3 functions via the RNF152/β-catenin signaling axis to repress TGF-β-dependent transcriptional responses in Xenopus early development.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301865","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":"Integrating miRNAs with QTL for identification of milk and reproduction related traits in dairy cattle.","authors":"Wonseok Shin, Seyoung Mun, Songmi Kim, Byung Sun Yu, Kornsorn Srikulnath, Kung Ahn, Kyudong Han","doi":"10.1007/s13258-025-01650-x","DOIUrl":"https://doi.org/10.1007/s13258-025-01650-x","url":null,"abstract":"<p><strong>Background: </strong>Dairy cattle are economically important animal resources contributing to human health and well-being by providing nutritious milk and other products. Non-coding RNAs are involved in biological processes, regulating gene expressions at the levels of messenger. However, the effects on miRNA expression and their function in dairy cattle are still unclear.</p><p><strong>Objective: </strong>We aimed to understand better miRNA expressions associated with milk and reproduction quantitative trait loci (QTLs) and their locations in dairy cattle.</p><p><strong>Methods: </strong>In this study, miRNA profiling was performed in blood samples collected from three non-pregnant cows using the Illumina HiSeq 2500 platform. The expression levels of miRNAs were estimated by miRDeep2 and QTLs associated with milk and reproduction were identified using cattleQTLdb. Functional enrichment analysis was performed to determine biological functions or pathways using DAVID.</p><p><strong>Results: </strong>In total, 406 known and 562 novel expressed miRNAs were identified in three dairy cattle using miRDeep2. A total of 27,652 and 31,064 QTLs associated with milk and reproduction traits were identified by QTL mapping for known and novel miRNAs, respectively. Of these, 1835 and 1020 miRNAs were related to milk and reproduction traits, respectively.</p><p><strong>Conclusion: </strong>Our study provides a basis for further research to understand the miRNA expressions in dairy cattle and their role in milk and reproduction traits. We suggest that miRNAs may be helpful as biomarkers for improving milk and reproduction traits in dairy cattle through genetic selection.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247526","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":"UBE2C regulating the lung carcinoma progression via inhibiting ubiquitin-proteasomal degradation to increase MMP9 protein stability.","authors":"Jie Zhao, Juanjuan Dai, Ning Zhou, Dongqin Liu, Dandan Wang, Shuang Miao, Chao Liang, Di An, Jiatong Jiang, Kaikai Gong, Yan Wu","doi":"10.1007/s13258-025-01623-0","DOIUrl":"10.1007/s13258-025-01623-0","url":null,"abstract":"<p><strong>Background: </strong>Non-small-cell-lung-cancer (NSCLC) is a prevalent lung malignancy among humans. UBE2C is a critical component of the ubiquitin-proteasome system, and its expression level is significantly associated with cancer development and cell proliferation. Nevertheless, the mechanisms of UBE2C in NSCLC remain unclear.</p><p><strong>Objective: </strong>We aimed to investigate the role of MMP9 in UBE2C-overexpressed NSCLC progression.</p><p><strong>Methods: </strong>The GEPIA database and Kaplan-Meier curves were used to determine UBE2C expression in human tumors and survival in NSCLC. CCK8, colony formation, and Transwell^® assays were employed to assess the function of UBE2C in vitro. Western blotting, immunofluorescence assay, and RT-qPCR were utilized to determine protein and mRNA expression levels. CHX chase and co-immunoprecipitation assays were used to elucidate the regulatory mechanism.</p><p><strong>Results: </strong>This research proved that UBE2C expression was related to patient overall survival, cell proliferation and migration. Furthermore, overexpressed UBE2C could promote the protein stability of Matrix metalloproteinase-9 (MMP9) to upregulate its protein level in NSCLC cells. Meanwhile, UBE2C upregulation promoted lung carcinoma progression by modulating MMP9 expression.</p><p><strong>Conclusions: </strong>Our findings indicate that UBE2C may be a therapeutic and prognostic target for lung carcinoma.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"651-662"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457591","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":"Comparison of unique Dong Tao chickens from Vietnam and Thailand: genetic background and differences for resource management.","authors":"Anh Huynh Luu, Trifan Budi, Worapong Singchat, Chien Phuoc Tran Nguyen, Thitipong Panthum, Nivit Tanglertpaibul, Thanyapat Thong, Kanithaporn Vangnai, Aingorn Chaiyes, Chotika Yokthongwattana, Chomdao Sinthuvanich, Kyudong Han, Narongrit Muangmai, Darren K Griffin, Michael N Romanov, Prateep Duengkae, Ngu Nguyen Trong, Kornsorn Srikulnath","doi":"10.1007/s13258-025-01644-9","DOIUrl":"10.1007/s13258-025-01644-9","url":null,"abstract":"<p><strong>Background: </strong>Rare Dong Tao (DT) chickens are a unique and highly productive poultry breed introduced from Vietnam to Thailand ~ 30 years ago. It has a very peculiar appearance, including enormously enlarged feet with reddish scales, and considered local and culturally significant to both countries. Their adaptability and distinct genetic traits have attracted global interest, underscoring their potential for breeding programs and a need for their thorough genetic makeup assessment.</p><p><strong>Objective: </strong>To assess the genetic diversity and differentiation within the Dong Tao chicken breed, comparing two populations introduced in Thailand with a native population in Vietnam.</p><p><strong>Methods: </strong>Three Dong Tao chicken populations from Thailand and Vietnam-along with 54 other indigenous, local chicken, and red junglefowl populations from Thailand, were analyzed using 28 microsatellite markers.</p><p><strong>Result: </strong>High genetic variability and low inbreeding levels were observed in these populations, indicating their effective management despite historical bottlenecks. Genetic similarities between DT-U and DT-HY and indigenous breeds, as well as the closer alignment of DT-L with red junglefowl, highlighted existing introgression and adaptation processes. Two markers, MCW0098 and MCW0216, showed a variation pattern due to potential impact of directional selection, possibly driven by environmental adaptation pressures. These findings emphasize the importance of DT chickens as genetic resources for breeding programs that focus on climate resilience and productivity enhancement.</p><p><strong>Conclusion: </strong>Dong Tao chickenshared genetic similarities with indigenous and local chicken breeds, and red junglefowl, with potential influence of directional selection driven by environmental adaptation pressures.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"727-739"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981475","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":"Comprehensive analysis based on IFN-γ and SASP related genes, bulk RNA and single-cell sequencing to evaluate the prognosis and immune landscape of stomach adenocarcinoma.","authors":"Jie Yang, Junwei Han","doi":"10.1007/s13258-025-01646-7","DOIUrl":"10.1007/s13258-025-01646-7","url":null,"abstract":"<p><strong>Background: </strong>Stomach adenocarcinoma (STAD) represents the predominant subtype of gastric cancer, known for its drug resistance, unfavorable prognosis, and low cure rates. IFN-γ serves as a cytokine generated by immune cells, instrumental in tumor immune clearance and essential to the tumor microenvironment. The aging-associated secretory phenotype (SASP) can modify the local tissue environment, facilitating gastric cancer progression and chemotherapy resistance.</p><p><strong>Objective: </strong>This study intends to identify STAD subtypes based on IFN-γ and SASP-related genes and to develop a risk prognostic model for predicting patient survival, tumor immune microenvironment, and responses to drug treatment.</p><p><strong>Methods: </strong>The genomic and clinical datasets originate from the Cancer Genome Atlas (TCGA) database, while the genes associated with IFN-γ and SASP come from pertinent scholarly articles. We discovered the prognostic genes linked to IFN-γ and SASP in STAD using Cox regression analysis. Next, we applied non-negative matrix factorization (NMF) to categorize LIHC into distinct molecular subtypes, identifying differentially expressed genes across these subtypes. Following this, we developed a predictive model using Cox and LASSO regression analyses to stratify patients into specific risk categories, validating the model to assess the prognostic significance of the identified signatures. Lastly, we integrated single-cell data to elucidate the immune landscape of STAD and identified potential drugs along with their sensitivity profiles.</p><p><strong>Results: </strong>We identified 17 prognostic genes related to IFN-γ and SASP, successfully classifying patients into two distinct molecular subtypes. These subtypes exhibited notable differences in immune profiles and prognostic outcomes. We pinpointed three differentially expressed genes to establish risk characteristics and created a prognostic model capable of accurately predicting patient outcomes. Our findings revealed a strong association between STAD and the extracellular matrix, low-risk group exhibited favorable prognosis, and may derive greater benefits from immunotherapy.</p><p><strong>Conclusion: </strong>We developed a risk model using IFN-γ and SASP-associated genes to predict the prognosis of STAD patients more accurately. Additionally, we assessed the immune landscape of STAD by integrating bulk RNA and single-cell sequencing analyses. This approach may yield valuable insights for clinical decision-making and immunotherapy strategies in STAD.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"777-796"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007595","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":"Genome-wide identification of NAC transcription factors in Acer paxii, and their expression dynamics during leaf aging.","authors":"Yuzhi Fei, Shah Faheem Afzal, Zhu Chen, Yue Zhao, Xin Meng, Jie Ren, Shuiming Zhang","doi":"10.1007/s13258-025-01638-7","DOIUrl":"10.1007/s13258-025-01638-7","url":null,"abstract":"<p><strong>Background: </strong>The NAC family (consisting of NAM, ATAF1/2, and CUC2) represents a crucial plant-specific transcription factor family, contributing significantly to various aspects of plant growth, development, and reactions to abiotic stresses. Yet, the underlying mechanism of NAC regulation in Acer paxii has not been discussed.</p><p><strong>Objectives: </strong>Identification of NAC genes (ApNACs) in the genome of Acer paxii and exploring the regulatory network of NACs in mediating leaf senescence.</p><p><strong>Methods: </strong>A thorough genome-wide analysis of the NAC gene family in the Acer paxii genome was performed.</p><p><strong>Results: </strong>We identified 117 ApNACs from the Acer paxii genome database, which were irregularly distributed across 13 chromosomes. Phylogenetic analysis revealed that ApNAC genes were partitioned into 16 subgroups. There are four kinds of cis-regulatory elements in the promoter region of the ApNACs gene. We compared the expression levels of ApNAC genes at different times using transcriptome data and selected six ApNAC genes for qRT-PCR, which the results showed basic consistency with the transcriptome results. Six ApNACs and 187 TFs from different families were selected, and it was found that the TF families with the highest correlation were WRKY, MYB, bZIP, and ERF, and these TF families were reported to participate in the regulation function in senescence.</p><p><strong>Conclusion: </strong>This study provides important data support for identifying the NAC gene family of Acer paxii and the regulatory function of the ApNAC genes on plant senescence, which will help to understand the NAC-mediated regulatory network in Acer paxii.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"671-686"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752374","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":"E3 ligase MIB1 regulates STAT1/P21 signaling via regulation of FGFR1 in colorectal cancer.","authors":"Chanhee Jung, Jieun Park, Sang Beom Seo","doi":"10.1007/s13258-025-01629-8","DOIUrl":"10.1007/s13258-025-01629-8","url":null,"abstract":"<p><strong>Background: </strong>Mind bomb 1 (MIB1) is an E3 ubiquitin ligase that promotes the polyubiquitination-mediated degradation of NOTCH ligands and plays an important role in various cancers by enhancing tumor cell proliferation. Also, MIB1 inhibited the cell cycle progression by transcriptional repression of P21 in HCT116 cells. Fibroblast growth factor receptor 1 (FGFR1) is a receptor tyrosine kinase (RTK) that plays a significant role in the progression of various cancers. However, the regulatory mechanisms underlying FGFR1-associated signaling in colon cancer remain unclear.</p><p><strong>Objective: </strong>We investigated whether MIB1 regulates protein stability of FGFR1 and impairs cell proliferation in HCT116 cells.</p><p><strong>Methods: </strong>We conducted immunoprecipitation assay to identify correlation of MIB1 and FGFR1. We also tested mRNA level of FGFR1 in MIB1-depleted HCT116 cells using reverse transcription-quantitative polymerase chain reaction. Furthermore, we transfected HA-MIB1 and FLAG-FGFR1 and analyzed the downstream signaling cascades by western blotting. Cell viability was assessed using colony formation assays and MTT assay.</p><p><strong>Results: </strong>FGFR1 interacts with MIB1 and controls FGFR1 protein level in HCT116 cells. Transcriptome analysis revealed that the mRNA levels of FGFR1 increased when MIB1 was depleted in HCT116 cells. Moreover, histone deacetylase 3 (HDAC3) is involved in histone deacetylation and transcriptional repression, mediating the interaction between MIB1 and FGFR1.</p><p><strong>Conclusion: </strong>These findings suggest the importance of MIB1-mediated transcriptional repression of FGFR1 and its potential therapeutic target in colon cancer.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"663-670"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596741","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":"Hippocampal MCT4 as a key regulator in excessive exercise-induced cognitive impairment: involvement of neuroinflammation.","authors":"Min Yeong Lee, Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim","doi":"10.1007/s13258-025-01642-x","DOIUrl":"10.1007/s13258-025-01642-x","url":null,"abstract":"<p><strong>Background: </strong>As human life expectancy increases, maintaining a healthy lifestyle has become crucial. However, excessive exercise (EE) can lead to negative consequences such as muscle damage and exercise addiction. Recently, numerous reports have indicated that EE negatively impacts cognitive performance, although the exact mechanism remains unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the specific mechanisms underlying cognitive alterations induced by EE.</p><p><strong>Methods: </strong>We conducted the Y-maze, Barnes maze, and Novel Object Recognition Test to assess both short-term and long-term memory, as well as object recognition ability. We then validated our findings using qRT-PCR to elucidate the underlying mechanisms. Additionally, Diclofenac (Dic), an anti-inflammatory drug, was administered to evaluate its effects on cognitive function and the results of the molecular experiments.</p><p><strong>Results: </strong>EE-induced mice exhibited cognitive impairments, along with elevated expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL) -6, and IL-1β, and downregulated monocarboxylate transporters (MCTs) like MCT4. However, animals pre-treated with Dic regained cognitive function, alongside restored levels of IL-6, IL-1β, and MCT4.</p><p><strong>Conclusion: </strong>MCT4 plays may play a crucial role in EE-induced cognitive impairments.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"717-726"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981528","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":"The GPR4 antagonist NE 52-QQ57 prevents ox-LDL-induced cellular senescence by promoting the expression of SIRT1.","authors":"Wei Luo, Jiming Zhou, Feng Liang, Xianghui Chou, Zhengliang Peng, Weihua Tan, Ziying Yu, Huan Wan","doi":"10.1007/s13258-024-01610-x","DOIUrl":"10.1007/s13258-024-01610-x","url":null,"abstract":"<p><strong>Background: </strong>Cell senescence-associated endothelia dysfunction is a vital point in the pathological progression of atherosclerosis (AS). G-protein coupled receptor 4 (GPR4) is a proton-sensing receptor involved in developing endothelial dysfunction.</p><p><strong>Objective: </strong>In this study, we investigated the protective role of NE 52-QQ57, a GPR4 inhibitor in endothelial cell senescence induced using an oxidized low-density lipoprotein (ox-LDL). We also unravel the underlying molecular mechanism of NE 52-QQ57 as a therapeutic agent.</p><p><strong>Methods: </strong>Endothelial cell senescence model was established using human aortic endothelial cells (HAECs) stimulated with ox-LDL. The expression levels of GPR4, p53, p16, and sirtuin1 (SIRT1) were evaluated using real-time PCR and western blot assays. ROS production was determined using dihydroethidium (DHE) staining. Further, interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) secretion and expression were determined using ELISA and real-time PCR analysis, respectively. Finally, β-galactosidase (SA-β-Gal) staining associated with cell senescence, telomerase activity, and cell cycle assay were used to determine the state of cell senescence.</p><p><strong>Results: </strong>Firstly, GPR4 was found to be upregulated in the ox-LDL-stimulated HAECs. We also identified elevated ROS, IL-6, and MCP-1 levels induced by ox-LDL and significantly abrogated by NE 52-QQ57 treatment. Second, a reversal in SA-β-Gal activity, telomerase activity, and G0/G1 proportion, with an upregulation in p53 and p16 expressions was observed on NE 52-QQ57 treatment in the ox-LDL induced model. Lastly, the decreased expression level of SIRT1 was extremely elevated by NE 52-QQ57. Notably, the inhibitory effect of NE 52-QQ57 against ox-LDL-induced cell senescence was abolished by the SIRT1 inhibitor EX-527.</p><p><strong>Conclusion: </strong>The GPR4 antagonist NE 52-QQ57 might prevent cellular senescence by promoting the expression of SIRT1.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"707-715"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965207","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}