Hereditas最新文献

{"title":"A bioinformatics analysis of the target role of miRNA-431-5p on KLK6 in colorectal cancer.","authors":"Juan Wang, Zonglang Lai, Na Liu, Yuhong Wang, Feng Li, Na Song, Jun Cheng","doi":"10.1186/s41065-025-00395-7","DOIUrl":"https://doi.org/10.1186/s41065-025-00395-7","url":null,"abstract":"<p><strong>Background: </strong>Although increasing evidence suggests that microRNAs (miRNAs) play different roles in the occurrence, development, and prognosis of colorectal cancer (CRC), investigations on miRNA-targeted regulation in CRC are sparse. However, the high morbidity and mortality of CRC necessitates exploring this area of research for potential alternative therapeutic approaches to CRC.</p><p><strong>Methods: </strong>Bioinformatics analysis was used to obtain the key Hub genes related to CRC, and survival analysis was performed to screen out the core genes. Meanwhile, verification was performed using CCK-8, Transwell, qPCR, WB, immunohistochemistry and dual luciferase assays at a cellular level.</p><p><strong>Results: </strong>This study identified the hub gene KLK6 associated with CRC based on the GEO and TCGA databases. Survival analysis revealed a significant decrease in the survival rate of CRC patients with increasing expression levels of KLK6. Target gene prediction confirmed that miR-431-5p can target KLK6. Cell experimental results demonstrated that the miR-431-5p inhibitor enhanced cell viability and promoted cell migration and invasion while miR-431-5p mimics reduced cell viability and inhibited cell migration and invasion. Both the inhibitor and mimics of miR-431-5p suppressed and promoted the expression of miR-431-5p, as well as promoted and inhibited the KLK6 mRNA and protein expression. Dual luciferase results showed that miR-431-5p targeted KLK6, and cell recovery experiments further verified that miR-431-5p regulated cell viability, migration and invasion by targeting KLK6.</p><p><strong>Conclusions: </strong>Through target gene prediction, miR-431-5p was found to target KLK6, suggesting its therapeutic potential in CRC. As such, therapies that can inhibit KLK6 via miR-431-5p offer a promising approach to CRC.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"46"},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742379","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 and functional characterization of key biomarkers in diffuse large B-cell lymphoma: emphasis on STYX as a prognostic marker and therapeutic target.","authors":"Junaid Abid, Basil A Mahmood Al-Rawi, Ahmad Mahmood, An Li, Tiemin Jiang","doi":"10.1186/s41065-025-00411-w","DOIUrl":"10.1186/s41065-025-00411-w","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBC) is the most common subtype of non-Hodgkin lymphoma, characterized by its aggressive nature and poor prognosis in advanced stages. Despite advances in treatment, the molecular mechanisms driving DLBC progression remain incompletely understood, necessitating the identification of novel biomarkers for diagnosis and prognosis. In this study, we analyzed two publicly available datasets (GSE32018 and GSE56315) from the Gene Expression Omnibus database (GEO) to identify overlapping differentially expressed genes (DEGs). Later on, a comprehensive in silico and in vitro methodology was adopted to decipher the role of identify DEGs in DLBC. DEGs analysis of GSE32018 and GSE56315 datasets identified five overlapping gene: SP3, CSNK1A1, STYX, SIRT5, and MGEA5. Expression validation using the GEPIA2 database confirmed the upregulation of SP3, CSNK1A1, STYX, and SIRT5, and the downregulation of MGEA5 in DLBC tissues compared to normal controls. Furthermore, mutational analysis revealed that CSNK1A1 was the only gene among these DEGs to exhibit mutations, with a 2.7% mutation frequency in DLBC patients. Methylation analysis highlighted a negative correlation between DEGs methylation levels and mRNA expression, while survival analysis identified high STYX expression as significantly associated with poorer overall survival in DLBC patients. Functional assays demonstrated that STYX knockdown in U2932 cells led to reduced cell proliferation, colony formation, and enhanced wound healing, indicating STYX's pivotal role in DLBC cell survival and migration. Additionally, gene enrichment analysis revealed the involvement of these DEGs in key biological processes, including intracellular trafficking and myeloid progenitor cell differentiation. These findings emphasize the potential of SP3, CSNK1A1, STYX, SIRT5, and MGEA5 as biomarkers and therapeutic targets in DLBC, particularly highlighting STYX as a promising prognostic marker and potential target for therapeutic intervention.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"45"},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700258","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":"Activation of TRAF1 induced by USP7/SP1 exacerbates the severity of infantile pneumonia.","authors":"Ying Liu, Yilun Ji, Yu Zhang, Zhengsi Li","doi":"10.1186/s41065-025-00410-x","DOIUrl":"10.1186/s41065-025-00410-x","url":null,"abstract":"<p><strong>Background: </strong>Infantile pneumonia (IP) is a leading cause of morbidity and mortality in children worldwide, with limited treatment options. Tumor necrosis factor receptor-associated factor 1 (TRAF1) has been implicated in the pathogenesis of various inflammatory diseases. Given the lack of effective therapies in IP, understanding the role of TRAF1 in regulating IP is crucial for developing new therapeutic strategies.</p><p><strong>Methods: </strong>This study utilized in vitro and in vivo models to investigate the role of TRAF1 in IP. WI-38 cells were stimulated with lipopolysaccharide (LPS), and rats were administered LPS to mimic IP. The mRNA expression of TRAF1 and Sp1 transcription factor (SP1) was analyzed using quantitative real-time polymerase chain reaction. The protein expression of TRAF1, ubiquitin-specific peptidase 7 (USP7), and SP1 was detected by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 assay and flow cytometry/TUNEL assays, respectively. Interleukin-6 and tumor necrosis factor-α levels were measured by enzyme-linked immunosorbent assays. Reactive oxygen species and malondialdehyde levels were analyzed using fluorescence microscopy and colorimetric assays. The interactions among USP7, TRAF1, and SP1 were identified using co-immunoprecipitation assay, immunofluorescence assay, and dual-luciferase reporter assay. TRAF1 silencing-induced effects were validated in a rat model. Lung tissue pathology was assessed using haematoxylin and eosin assay and Massion assay.</p><p><strong>Results: </strong>LPS treatment induced apoptosis, inflammation, and oxidative stress of WI-38 cells, however, TRAF1 silencing ameliorated these effects. USP7 stabilized TRAF1 protein expression through its deubiquitinating activity, while TRAF1 overexpression reversed the effects of USP7 silencing in LPS-treated WI-38 cells. In addition, SP1 transcriptionally activated TRAF1 in WI-38 cells. Further, TRAF1 silencing improved lung injury in LPS-induced mice.</p><p><strong>Conclusion: </strong>Activation of TRAF1 by USP7/SP1 exacerbated the severity of IP, suggesting that targeting TRAF1 may have significant clinical implications for the treatment of IP.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"44"},"PeriodicalIF":2.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692007","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":"Mechanistic insights into CDCA gene family-mediated glioblastoma progression: implications for diagnosis, prognosis, and therapeutic targeting.","authors":"Chang Liu","doi":"10.1186/s41065-025-00415-6","DOIUrl":"10.1186/s41065-025-00415-6","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a highly aggressive brain tumor characterized by poor prognosis and limited therapeutic options. Understanding the molecular mechanisms driving GBM progression is essential for developing more effective diagnostic and therapeutic approaches. Specifically, investigating Cell Division Cycle-Associated (CDCA) genes offers new perspectives on cell cycle regulation and the proliferation of GBM cells, which are key factors in tumor growth and resistance to treatment. These genes have not been extensively studied in GBM, making them a promising area for targeted research and potential therapeutic interventions. This project was launched to elucidate the pathogenic, diagnostic, and therapeutic roles of CDCA genes in GBM.</p><p><strong>Methodology: </strong>Total RNA was extracted from GBM cell lines followed by RT-qPCR to analyze the expression of CDCA genes. The expression validation, prognostic significance, and mutational analysis of CDCA genes were performed using various databases. Functional assays, including gene knockdown, colony formation, proliferation, and wound healing, were conducted in U87MG cells to assess the role of CDCA7 and CDCA8 in GBM.</p><p><strong>Results: </strong>The expression analysis of CDCA genes in 12 GBM cell lines and 6 normal brain cell lines revealed significant overexpression of these genes in GBM. ROC curve analysis demonstrated excellent diagnostic potential, with AUC values of 1 for most genes. This indicates that CDCA gene expression effectively distinguishes GBM cells from normal brain cells. Validation using additional TCGA data confirmed the upregulation of these genes in GBM tumors, with significant association to key cancer-related pathways. Survival analysis showed that higher expression of CDCA genes correlated with poor prognosis in GBM patients. Mutation, CNV, and methylation analyses revealed alterations in these genes, further supporting their role in GBM. Additionally, CDCA gene expression was linked to immune modulation and cell cycle-related functions, suggesting their involvement in immune evasion and tumor proliferation. Knockdown experiments of CDCA7 and CDCA8 in U87MG cells demonstrated a reduction in cell proliferation, colony formation, and migration, highlighting their potential as therapeutic targets.</p><p><strong>Conclusion: </strong>Overall, our findings suggest that CDCA genes could serve as both diagnostic biomarkers and therapeutic targets for GBM.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"43"},"PeriodicalIF":2.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669790","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":"Construction of a ferroptosis-based prediction model for the prognosis of MYCN-amplified neuroblastoma and screening and verification of target sites.","authors":"Linjun Tan, Guoqian He, Chengqi Shen, Sijia He, Yan Chen, Xia Guo","doi":"10.1186/s41065-025-00413-8","DOIUrl":"10.1186/s41065-025-00413-8","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma (NB) is a prevalent extracranial solid tumor in pediatric patients. Of these, the MYCN-amplified type has a poor treatment response and prognosis. To enhance therapeutic efficacy and prognostic outcomes, numerous research teams have undertaken extensive investigations through various pathways and directions. Among these, ferroptosis has recently emerged as a significant area of research focus.Ferroptosis, a type of iron-dependent cell death, is primarily caused by lipid peroxides. This study intends to develop a prognosis model based on MYCN-amplified NB and ferroptosis-related genes (FGs).</p><p><strong>Methods: </strong>Data for this study were sourced from the TARGET and FerrDb databases. Lasso regression algorithms and univariate COX analysis were leveraged to determine feature genes; multivariate COX analysis was employed to develop a prediction model and risk scores; and receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were utilized to assess the predictive ability of the model. Furthermore, discrepancies in immune cell infiltration (ICI) between the high-risk (HR) and low-risk (LR) populations were assessed via CIBERSORT analysis. Finally, experiments were conducted on MYCN-amplified and MYCN non-amplified cells so as to validate the differential expression of the gene.</p><p><strong>Results: </strong>A prediction model was constructed and risk scores were calculated based on 4 genes (LIFR, TP53, NRAS, and OSBPL9). The HR group, which was stratified by the median score, had a lower overall survival rate than the LR group.The differences in expression of each gene between MYCN-amplified and MYCN non-amplified cells were further confirmed through cell experiments and qPCR.</p><p><strong>Conclusion: </strong>The prediction model in this study can be employed to forecast the prognosis of MYCN-amplified NB. These genes may represent promising new ferroptosis-related intervention targets (FITs) in treating MYCN-amplified NB, with the potential to improve patient outcomes.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"41"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663197","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":"ADME gene-driven prognostic model for bladder cancer: a breakthrough in predicting survival and personalized treatment.","authors":"Haojie Dai, Xi Zhang, You Zhao, Jun Nie, Zhenyu Hang, Xin Huang, Hongxiang Ma, Li Wang, Zihao Li, Ming Wu, Jun Fan, Ke Jiang, Weiping Luo, Chao Qin","doi":"10.1186/s41065-025-00409-4","DOIUrl":"10.1186/s41065-025-00409-4","url":null,"abstract":"<p><strong>Background: </strong>Genes that participate in the absorption, distribution, metabolism, excretion (ADME) processes occupy a central role in pharmacokinetics. Meanwhile, variability in clinical outcomes and responses to treatment is notable in bladder cancer (BLCA).</p><p><strong>Methods: </strong>Our study utilized expansive datasets from TCGA and the GEO to explore prognostic factors in bladder cancer. Utilizing both univariate Cox regression and the lasso regression techniques, we identified ADME genes critical for patient outcomes. Utilizing genes identified in our study, a model for assessing risk was constructed. The evaluation of this model's predictive precision was conducted using Kaplan-Meier survival curves and assessments based on ROC curves. Furthermore, we devised a predictive nomogram, offering a straightforward visualization of crucial prognostic indicators. To explore the potential factors mediating the differences in outcomes between high and low risk groups, we performed comprehensive analyses including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based enrichment analyses, immune infiltration variations, somatic mutation landscapes, and pharmacological sensitivity response assessment etc. Immediately following this, we selected core genes based on the PPI network and explored the prognostic potential of the core genes as well as immune modulation, and pathway activation. And the differential expression was verified by immunohistochemistry and qRT-PCR. Finally we explored the potential of the core genes as pan-cancer biomarkers.</p><p><strong>Results: </strong>Our efforts culminated in the establishment of a validated 17-gene ADME-centered risk prediction model, displaying remarkable predictive accuracy for BLCA prognosis. Through separate cox regression analyses, the importance of the model's risk score in forecasting BLCA outcomes was substantiated. Furthermore, a novel nomogram incorporating clinical variables alongside the risk score was introduced. Comprehensive studies established a strong correlation between the risk score and several key indicators: patterns of immune cell infiltration, reactions to immunotherapy, landscape of somatic mutation and profiles of drug sensitivity. We screened the core prognostic gene CYP2C8, explored its role in tumor bioregulation and validated its upregulated expression in bladder cancer. Furthermore, we found that it can serve as a reliable biomarker for pan-cancer.</p><p><strong>Conclusion: </strong>The risk assessment model formulated in our research stands as a formidable instrument for forecasting BLCA prognosis, while also providing insights into the disease's progression mechanisms and guiding clinical decision-making strategies.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"42"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663207","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":"Screening and analysis of programmed cell death related genes and targeted drugs in sepsis.","authors":"Juanjuan Song, Kairui Ren, Yi Wang, Dexin Zhang, Lin Sun, Zhiqiang Tang, Lili Zhang, Ying Deng","doi":"10.1186/s41065-025-00403-w","DOIUrl":"10.1186/s41065-025-00403-w","url":null,"abstract":"<p><strong>Objective: </strong>This study employed bioinformatics techniques to identify diagnostic genes associated with programmed cell death (PCD) and to explore potential therapeutic agents for the treatment of sepsis.</p><p><strong>Methods: </strong>Gene expression profiles from sepsis patients were analyzed to identify differentially expressed genes (DEGs) and hub genes through Weighted Gene Co-expression Network Analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the functions of the DEGs. PCD-related genes were cross-referenced with the identified DEGs. Diagnostic genes were selected using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) methodologies. Single-cell RNA sequencing was utilized to assess gene expression in blood cells, while CIBERSORT was employed to evaluate immune cell infiltration. A transcription factor (TF)-microRNA (miRNA)-hub gene network was constructed, and potential therapeutic compounds were predicted using the Drug Gene Interaction Database (DGIdb). Mendelian Randomization (MR) methods were applied to analyze genome-wide association study (GWAS) data for S100A9, TXN, and GSTO1.</p><p><strong>Results: </strong>The analysis revealed 2156 PCD-related genes, 714 DEGs, and 1198 hub genes, with 88 genes enriched in immune and cell death pathways. Five pivotal PCD-related genes (IRAK3, S100A9, TXN, NFATC2, and GSTO1) were identified, leading to the construction of a network comprising six transcription factors and 171 microRNAs. Additionally, seven drugs targeting S100A9, TXN, and NFATC2 were identified. MR analysis suggested that a decrease in GSTO1 levels is associated with an increased risk of sepsis, and that sepsis influences the levels of S100A9, TXN, and GSTO1.</p><p><strong>Conclusions: </strong>Through bioinformatics approaches, this study successfully identified five genes (IRAK3, S100A9, TXN, NFATC2, and GSTO1) associated with programmed cell death in the context of sepsis. This research identified seven candidate drugs for sepsis treatment and established a methodological framework for predicting biomarkers and drug targets that could be applicable to other diseases.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"40"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663221","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":"Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma.","authors":"Feng Shen, Xing Liu, Fengjiao Ding, Zhonglin Yu, Xinyi Shi, Lushan Cheng, Xuewei Zhang, Chengbao Jing, Zilong Zhao, Hongyou Cao, Bing Zhao, Jing Liu","doi":"10.1186/s41065-025-00398-4","DOIUrl":"10.1186/s41065-025-00398-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Esophageal squamous cell carcinoma (ESCA) is a type of cancer that starts in the cells lining the esophagus, the tube connecting the throat to the stomach. It is known for its aggressive nature and poor prognosis. Understanding the key factors that drive this cancer is crucial for developing better diagnostic tools and treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Gene expression profiles of ESCA were analyzed using Gene Expression Omnibus (GEO) datasets (GSE23400, GSE29001, GSE92396, and GSE1420) from the GEO database. Differentially expressed genes (DEGs) were identified using the limma package, and a protein-protein interaction (PPI) network was constructed using the STRING database. Hub genes were identified based on the degree method. Further validation was performed through reverse transcription quantitative PCR (RT-qPCR), mutational and copy number variation (CNV) analysis via the cBioPortal database, promoter methylation analysis using the OncoDB and GSCA databases, survival analysis, immune infiltration analysis through the GSCA database, and functional assays, including knockdown of key genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified four key hub genes, COL3A1, COL4A1, COL5A2, and CXCL8 that play significant roles in ESCA. These genes were highly expressed in ESCA tissues and cell lines, with expression levels significantly (p-value &lt; 0.001) elevated compared to normal controls. Receiver operating characteristic (ROC) curve analysis revealed exceptional diagnostic performance for all four genes, with area under the curve (AUC) values of 1.0, indicating perfect sensitivity and specificity in distinguishing ESCA from normal controls. Mutational analysis revealed that COL3A1 was altered in 67% of ESCA samples, primarily through missense mutations, while COL5A2 exhibited alterations in 50% of the samples, including splice site and missense mutations. Additionally, gene amplification patterns were observed in all four hub genes, further validating their oncogenic potential in ESCA progression. A significant (p-value &lt; 0.05) promoter hypomethylation was detected in these genes, suggesting a potential regulatory role in their expression. Functional assays demonstrated that knocking down COL3A1 and COL4A1 led to decreased cell proliferation, colony formation, and migration, indicating their critical roles in tumor progression. Additionally, these genes were involved in pathways related to the extracellular matrix and immune system modulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;COL3A1, COL4A1, COL5A2, and CXCL8 are crucial in ESCA development and progression, particularly in remodeling the extracellular matrix, modulating the immune system, and promoting metastasis. These findings suggest that these genes could serve as potential biomarkers for diagnosing ESCA and targets for future therapies. Future research should focus on in vivo validation of these findings and clinical testing to assess the therapeutic pot","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"38"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633999","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":"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}