Hereditas最新文献

{"title":"CircCENPM serves as a CeRNA to aggravate nasopharyngeal carcinoma metastasis and stemness via enhancing BMI1.","authors":"Rui Wang, Fei Wang","doi":"10.1186/s41065-025-00406-7","DOIUrl":"10.1186/s41065-025-00406-7","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with high mortality and dismal prognosis. Emerging research have disclosed that circRNAs are crucial gene expression regulators engaged in tumor advancement. This work aspired to identify novel oncogenic circRNA driving NPC progression.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed to explore and predict underlying circRNA and downstream targets. Luciferase reporter assay was executed to check the binding relationship between these genes. Cell function tests were conducted using CCK-8, would healing, and flow cytometry. The stemness markers CD133, Nanog and Oct4 was detected via western blot.</p><p><strong>Results: </strong>CircCENPM was notably enhanced in NPC. Silencing of circCENPM suppressed NPC cell growth, migration, and stemness in vitro, simultaneously impeded tumorigenesis of NPC in vivo. Moreover, circCENPM could interact with miR-362-3p, whereas miR-362-3p inhibitor apparently reversed the mitigated growth and stemness induced by circCENPM knockdown in NPC cells. Furthermore, BMI1 was identified to be the downstream target of miR-362-3p, and BMI1 introduction partially offset the anti-tumor function of miR-362-3p in NPC cells.</p><p><strong>Conclusion: </strong>CircCENPM functioned as a carcinogenic driver and facilitated NPC growth and stemness via miR-362-3p/BMI1 regulatory network, which provided a potential biomarker and attractive target for NPC intervention and treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"39"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association between blood metabolites and head and neck cancer: butyrylcarnitine identified as an associated trait for cancer risk and progression.","authors":"Ying Li, Zihan Chen, Zongwei Huang, Jing Wang, Jue Wang, Lanxin Lin, Ruyu Lin, Jinghua Lai, Libin Zhang, Sufang Qiu","doi":"10.1186/s41065-025-00408-5","DOIUrl":"10.1186/s41065-025-00408-5","url":null,"abstract":"<p><strong>Background: </strong>Blood metabolites play an important role in predicting or influencing the occurrence and development of cancers. We aimed to evaluate the relationship between blood metabolites and the occurrence of head and neck cancer (HNC).</p><p><strong>Methods: </strong>We employed a Mendelian randomization (MR) approach to investigate the role of blood metabolites in HNC predisposition. The HNC cell line HN30 was treated with butyrylcarnitine, the metabolite identified through MR analysis, and subjected to a series of cellular assays to assess its potential carcinogenic effects.</p><p><strong>Results: </strong>Among the 258 blood metabolites analyzed, butyrylcarnitine emerged as the only metabolite demonstrating a potential causal association with HNC risk following Bonferroni correction (inverse-variance-weighted MR method: β = 0.904, P < 0.001). Genetically predicted higher levels of butyrylcarnitine (log-transformed) were causally linked to an increased risk of HNC (OR: 2.470, 95% CI: 1.530-3.987). Sensitivity analyses, including MR-Egger regression, leave-one-out analysis, and funnel plots, confirmed the robustness of the findings, with no evidence of directional pleiotropy. In vitro experiments further demonstrated that butyrylcarnitine promoted the proliferation, migration and invasion of HN30 cells.</p><p><strong>Conclusions: </strong>By employing a genetic epidemiological framework, our research assessed the impact of metabolite butyrylcarnitine on HNC susceptibility. These findings offer valuable insights into potential therapeutic targets and highlight the promise of targeted metabolic strategies for reducing HNC risk. Nevertheless, further research is required to elucidate the precise biological mechanisms underlying these findings.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"36"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-33 as a novel diagnostic biomarker for distinguishing cholesterol from adenomatous polyps: a case-control study.","authors":"Xia Hu, Ping Zhang, Tong Wang, Quanzhi Li, Minjia Li, Zhuohan Zhao, Rui Yu, Yan Tan, Chengli Yao","doi":"10.1186/s41065-025-00407-6","DOIUrl":"10.1186/s41065-025-00407-6","url":null,"abstract":"<p><p>Cholecystectomy is often excessively utilized in the management of gallbladder polyps. It is crucial to effectively differentiate between adenomatous and cholesterol polyps to reduce unnecessary cholecystectomies. This study aimed to investigate the potential of miR-33 as a novel diagnostic biomarker for distinguishing cholesterol from adenomatous polyps. Gallbladder specimens were retrospectively collected from gallbladder polyp patients who underwent laparoscopic cholecystectomy at the Second Department of General Surgery, Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, between June 2021 and December 2021. Pathological analysis categorized the specimens into two groups: the cholesterol polyp group (n = 13) and the adenomatous polyp group (n = 12). The expression levels of miR-33a and miR-33b in both groups were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). MiR-33a level and the miR-33a/miR-33b ratio were significantly lower in cholesterol polyps than in adenomatous polyps (p < 0.05). Spearman correlation analysis showed a strong positive correlation between miR-33a and miR-33b (r = 0.956, p < 0.001). Stepwise logistic regression analysis revealed that decreased miR-33b and elevated miR-33a/miR-33b ratio are independent risk factors for cholesterol polyps (p < 0.05). A predictive model was constructed, with the model's AUC for diagnosing adenomatous polyps being 0.885 (95% CI: 0.753-1.000, p = 0.001), exhibiting a notable specificity of 84.62% and a sensitivity of 83.33% at a cut-off of 0.424. MiR-33 could serve as a novel diagnostic biomarker for distinguishing cholesterol from adenomatous polyps to facilitate the diagnosis and treatment of clinicians.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"37"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m⁶A transferase KIAA1429 mediates the upregulation of LncRNA LINC00968 promoting the progression of gastric cancer cells.","authors":"Huijun Liu, Menghan Yang, Chunyue Zhang, Yanmin Zhang, Yan Wang, Yueda Chen","doi":"10.1186/s41065-025-00393-9","DOIUrl":"10.1186/s41065-025-00393-9","url":null,"abstract":"<p><strong>Background: </strong>The screening and monitoring of gastric cancer is still a clinical challenge. Both N⁶-methyladenosine (m⁶A) and lncRNAs have been evidenced as critical regulators of gastric cancer, but their interaction and potential in modulating tumor progression remain unclear. This study aimed to evaluate the function of lncRNA LINC00968 in gastric cancer biological processes, and we discovered the role of KIAA1429, a typical m⁶A eraser, in mediating LINC00968 function.</p><p><strong>Materials and methods: </strong>The expression of LINC00968 was assessed using PCR and regulated by cell transfection. Cellular processes were evaluated by CCK8 and Transwell assays. The m⁶A modification and the interaction of LINC00968 with KIAA1429 were identified with Methylated RNA immunoprecipitation-qPCR. The regulatory effect of LINC00968 on miR-3202 and VIRMA was estimated by luciferase reporter assay.</p><p><strong>Results: </strong>Significantly increased LINC00968 was observed in gastric cancer cells. Silencing LINC00968 suppressed gastric cancer cell growth and motility. m⁶A-modified sites were predicted in LINC00968 and overexpressing KIAA1429 enhanced the enrichment and stability of LINC00968 in gastric cancer and reversed the knockdown of LINC00968. The overexpression of KIAA1429 could attenuate the inhibitory effect of LINC00968 knockdown on gastric cancer cellular processes. LINC00968 could negatively regulate the expression of miR-3202, which further regulate VIRMA, the coding gene of KIAA1429, in gastric cancer cells.</p><p><strong>Conclusions: </strong>LINC00968 contributes to the enhanced cell growth and metastasis of gastric cancer, which was mediated by KIAA1429-mediating m⁶A modification and the miR-3202/VIRMA axis.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"34"},"PeriodicalIF":2.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of regulator gene and pathway in myocardial ischemia-reperfusion injury: a bioinformatics and biological validation study.","authors":"Yanqi Liu, Xiaodong Sheng, Zhenghong Zhao, Hongxia Li, Jiahui Lu, Lihuan Xie, Guanqun Zheng, Tingbo Jiang","doi":"10.1186/s41065-025-00397-5","DOIUrl":"10.1186/s41065-025-00397-5","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) is the primary cause of cardiac mortality worldwide. However, myocardial ischemia-reperfusion injury (MIRI) following reperfusion therapy is common in AMI, causing myocardial damage and affecting the patient's prognosis. Presently, there are no effective treatments available for MIRI.</p><p><strong>Methods: </strong>We performed a comprehensive bioinformatics analysis using three GEO datasets on differentially expressed genes, including gene ontology (GO), pathway enrichment analyses, and protein-protein interaction (PPI) network analysis. Cytoscape and LASSO methods were employed to identify novel regulator genes for ischemia-reperfusion (I/R). Notably, gene S100A9 was identified as a potential regulator of I/R. Additionally, clinical sample datasets were analyzed to prove the expression and mechanism of S100A9 and its down genes in I/R. The correlation of S100A9 with cardiac events was also examined to enhance the reliability of our results.</p><p><strong>Results: </strong>We identified 135 differential genes between the peripheral blood of 47 controls and 92 I/R patients. S100A9 was distinguished as a novel regulator gene of I/R with diagnostic potential. RT-qPCR test demonstrated significant upregulation of S100A9 in I/R. We also verified that S100A9 expression strongly correlates with left ventricular ejection fraction (LVEF) and MIRI.</p><p><strong>Conclusion: </strong>This study confirms that S100A9 is a key regulator of I/R progression and may participate in ischemia-reperfusion injury by upregulating RAGE /NFKB-NLRP3 activation. Elevated S100A9 levels may serve as a marker for identifying high-risk MIRI patients, especially those with coronary artery no-reflow (CNR), who might benefit from targeted therapeutic interventions. Furthermore, Peripheral blood S100A9 in AMI represents a new therapeutic target for preventing MIRI.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"35"},"PeriodicalIF":2.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacological approach combined with weighted gene co-expression network analysis identifies CDKN2A as the keg target of Changweiqing against colorectal cancer.","authors":"Ma Zushuai, Ji Yanrong, Zhao Chengdu, Zhu Xu, Ding Qianshan","doi":"10.1186/s41065-025-00405-8","DOIUrl":"10.1186/s41065-025-00405-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Changweiqing (CWQ) is a Chinese herbal formula for the treatment of the gastrointestinal tract diseases, but its role in the treatment of colorectal cancer (CRC) has not been clarified. This study aimed to explore the molecular mechanism of CWQ in CRC treatment through bioinformatics analysis and network pharmacology.</p><p><strong>Methods: </strong>Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction database were used to collect the bioactive components of CWQ. The databases including DisgeNET, GeneCards, MalaCards, Online Mendelian Inheritance in Man and Comparative Toxicogenomics were used to obtain CRC-related targets. The Cancer Genome Atlas - colon adenocarcinoma dataset was used to obtain prognosis-related genes in CRC based on weighted gene co-expression network analysis (WGCNA). A protein-protein interaction network was constructed to screen core targets, with STRING database and Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking was performed with AutoDock Vina software. Core targets were further analyzed using Gene Expression Profiling Interactive Analysis platform, Human Protein Atlas database, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and GeneMANIA database. In vitro experiments were further performed to investigate the effects of quercetin, one of the main components of CWQ, on CRC cells.</p><p><strong>Results: </strong>6356, 1901 and 2980 CRC-related genes were obtained from differential expression analysis, WGCNA and open access databases, respectively. CWQ contained a total of 70 bioactive ingredients, of which 64 ingredients had a total of 836 therapeutic targets. Functional enrichment analysis indicated that CWQ may be involved in regulating pathways in cancer, MAPK signaling pathway and AGE-RAGE signaling pathway, and further analysis identified 14 core targets of CWQ. These core targets were significantly correlated with cell cycle, p53 signaling pathway, FoxO signaling pathway and pathways in cancer. Among these core targets, cyclin-dependent kinase inhibitor 2 A (CDKN2A) expression was closely associated with shorter overall survival and clinical stage of CRC patients. The main bioactive ingredients of CWQ targeting CDKN2A were quercetin, luteolin, kaempferol, isorhamnetin, 7-O-methylisomucronulatol and 7-Methoxy-2-methyl isoflavone. Additionally, quercetin caused G0/G1 phase arrest and inhibited the viability of CRC cells.</p><p><strong>Conclusion: </strong>The active ingredients of CWQ may play an anti-CRC role through multi-targets and multi-pathways, regulating the cell cycle and cell viability of CRC cells.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"33"},"PeriodicalIF":2.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0006006 is a potential biomarker for prognosis and cisplatin resistance in non-small cell lung cancer.","authors":"Min Ding, Jing Zhao, XiaoNa Li","doi":"10.1186/s41065-025-00392-w","DOIUrl":"10.1186/s41065-025-00392-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Platinum-based drugs, such as cisplatin (DDP), are the standard treatment, yet drug resistance has become a key challenge. Previous studies have shown that hsa_circ_0006006 promotes non small cell lung cancer (NSCLC) progression. This study aimed to reveal the role of specific circRNAs in DDP resistance in NSCLC and their potential clinical applications.</p><p><strong>Methods: </strong>CircRNA sequencing data of three NSCLC tissue and three normal tissue samples were extracted from the GEO database based on conditions that matched the microarray expression profiles of circRNAs from human NSCLC lung samples and matched neighboring samples and raw matrix data and platform annotation data, and differential expression analysis was performed using the R language. Log2 Fold change > 1 and P < 0.05 were labeled as differential genes. Serum samples were collected from 31 NSCLC patients and 21 DDP-resistant NSCLC patients. The Kaplan-Meier method was used to detect the correlation between circRNA levels and survival prognosis of NSCLC patients. The relationship between circRNAs and clinicopathological characteristics of patients was assessed by chi-square test. RT-qPCR was performed to detect the expression of key circRNAs associated with DDP drug resistance. circRNAs were analyzed by ROC curves to assess the diagnostic potential. A549 cells and A549/DDP cells were cultured to verify the effect of up- and down-regulation of hsa_circ_0006006 on DDP drug resistance in NSCLC cells using colony formation assay and flow cytometry.</p><p><strong>Results: </strong>Abnormally elevated hsa_circ_0006006 expression was closely associated with NSCLC survival prognosis as well as DDP resistance (p < 0.05) with good diagnostic efficacy (AUC for NSCLC = 0.91, p < 0.01; AUC for DDP resistant = 0.80, p = 0.00). This was further validated in the analysis of clinical samples (p < 0.05). Knockdown of hsa_circ_0006006 significantly reduced DDP resistance in NSCLC cells, while overexpression of hsa_circ_0006006 had the opposite effect (p < 0.05).</p><p><strong>Conclusion: </strong>NSCLC survival prognosis is associated with aberrant expression of hsa_circ_0006006, which regulates NSCLC cell proliferation and apoptosis and thus promotes DDP drug resistance. These findings provide potential targets for patient prognosis and assessment of biomarkers of response to DDP therapies that can be used to aid in early diagnosis and prognostic assessment, as well as new options for the future development of relevant small-molecule inhibitors or nucleic acid drugs.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"32"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the effects of global gene knockout of MrgF on motor performance and pain sensitivity in mice.","authors":"Xuejiao Chen, Yan Chen, Runzhe Shu, Shunyuan Lu, Ming-Min Gu, Chunling Shen, Zhugang Wang, Xiaofang Cui","doi":"10.1186/s41065-025-00377-9","DOIUrl":"10.1186/s41065-025-00377-9","url":null,"abstract":"<p><p>Mas-related G protein-coupled receptors (Mrgs) are a subset of GPCRs linked to pain modulation. MrgF was identified as an orphan Mrg whose function and ligand remain unclear. In this study, in addition to its expression in the dorsal root ganglia (DRG), the primary afferent center that transmits pain, we identified dense expression of MrgF, particularly concentrated in the Purkinje cell layer of the mouse cerebellum. Given the the important role of Purkinje neurons in both motor modulation and non-motor modulation, including pain processing, we established a MrgF knockout mouse (MrgF^-/-) model and performed a battery of behavioral tests to explore motor performance and assess pain-associated responses. MrgF^-/- mice exhibited no disturbances in coordination and motor balance during the rotarod, pole, balance beam, and treadmill tests, and normal cerebellar histology was retained. In hot plate assays, MrgF^-/- mice displayed reduced pain-related behavioral responses to thermal stimuli, although no significance differences were found in tail flick assays between MrgF^-/- and wild-type (wt) mice. Moreover, in formalin tests, MrgF^-/- mice also showed decreased chemical-induced nociception. This was accompanied by a downregulation in the expression levels of genes associated with nociceptive modulation, such as c-fos, Runx1, Nav1.7, Nav1.8, and Nav1.9, within the DRG of MrgF^-/- mice. Taken together, our findings suggest that MrgF may play a significant role in modulating pain sensitivity, thereby advancing the understanding of the functional characteristics of the Mrgs family.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"31"},"PeriodicalIF":2.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pathogenic NR2F1 gene variant disrupts transcriptional activity and causes severe neurodevelopmental delay in Bosch-Boonstra-Schaaf syndrome.","authors":"Juan Liu, Jihong Hu, Pingqiu Zhou, Yaqin Duan, Shuigui Yin","doi":"10.1186/s41065-025-00394-8","DOIUrl":"10.1186/s41065-025-00394-8","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear receptor subfamily 2, group F, member 1 (NR2F1) gene variations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome. The NR2F1 genotype correlates with its phenotype; variants within the DNA-binding domain may cause severe psychomotor developmental disorders. However, the mechanisms underlying these phenotypes remain unclear.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed on the proband and her parents DNA. Candidate variants were verified by Sanger sequencing and bioinformatics analyses. Molecular dynamics simulations were performed to predict structural changes in the mutant NR2F1 protein. A dual-luciferase assay was used to analyze the variant's effect on transcriptional activation.</p><p><strong>Results: </strong>The proband was a 10-month-old girl with severe motor and cognitive developmental delays accompanied by bilateral optic nerve pallor. Genetic testing revealed a novel NR2F1 gene variant, NM_005654.6: c.452T > A (p.Met151Lys). Bioinformatics analysis suggested that this variant alters the protein structure or function. The molecular dynamics analysis showed that this variant might affect the stability of the zinc finger structure within the NR2F1 DNA-binding domain. Dual-luciferase assays indicated this variant affects transcriptional activation.</p><p><strong>Conclusions: </strong>The NR2F1 variant c.452T > A (p.Met151Lys) may genetically cause the severe clinical phenotypes observed in this patient. This finding expands the spectrum of NR2F1 variants.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"30"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIN1 inhibited tumor growth, metastasis and stemness by ALDH1/NOTCH pathway in bladder carcinoma.","authors":"Si-Yu Chen, Ya-Long Zhang, Xiao-Ran Li, Ji-Rong Wang, Kun-Peng Li, Shun Wan, Jian-Wei Yang, Hao Wang, Jin-Long Cao, Chen-Yang Wang, Xin-Peng Fan, Sheng-Jun Fu, Li-Yun Ding, Tuan-Jie Che, Li Yang","doi":"10.1186/s41065-025-00384-w","DOIUrl":"10.1186/s41065-025-00384-w","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) represents one of the most prevalent urological malignancies worldwide. Bridging integrator 1 (BIN1), a well-characterized tumor suppressor that interacts with and inhibits oncogenic Myc transcription factors, has demonstrated crucial roles in various cancer types. However, its specific functions and underlying molecular mechanisms in BLCA development and progression remain poorly understood. This study aims to elucidate the role of BIN1 in regulating BLCA cell proliferation, metastasis, and cancer stem cell properties.</p><p><strong>Methods: </strong>Using urinary proteomics analysis, we identified BIN1 as a significantly dysregulated protein in BLCA. The clinical significance of BIN1 was further validated through comprehensive analyses of public databases. BIN1 expression levels defined distinct molecular and immunological subtypes of BLCA. Through proteomic profiling of BIN1-overexpressing UMUC3 cells and corresponding controls, we identified ALDH1 as a key downstream effector in the BIN1-regulated ALDH1/NOTCH signaling axis. We employed multiple experimental approaches, including Western blot analysis, quantitative RT-PCR, immunofluorescence staining, wound healing assays, transwell migration assays, colony formation assays, tumor sphere formation assays, flow cytometry, CCK8 proliferation assays, and cell transfection experiments.</p><p><strong>Results: </strong>We observed significant downregulation of BIN1 in both BLCA tissues and cell lines compared to normal adjacent tissues and SV-HUC-1 cells, respectively. BIN1 overexpression inhibited cancer cell proliferation by promoting apoptosis and suppressed epithelial-mesenchymal transition (EMT), thereby reducing local invasion and distant metastasis. Additionally, BIN1 regulated cancer stem cell properties through modulation of ALDH1 expression, with NOTCH2 acting as a crucial downstream mediator of ALDH1 signaling.</p><p><strong>Conclusion: </strong>Our findings demonstrate that BIN1 functions as a tumor suppressor in BLCA and suggest its potential utility as both a diagnostic biomarker and therapeutic target for BLCA treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"29"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}