Discover. Oncology最新文献

{"title":"Integrating Mendelian randomization and multi-transcriptomic analyses to unveil the genetic association risk of regulatory T cell-mediated free cholesterol and gastric cancer.","authors":"Fanyu Peng, Haitao Liu, Yesong Guo, Jing Wen, Yizhi Ge, Yanhong Luo","doi":"10.1007/s12672-025-02739-1","DOIUrl":"10.1007/s12672-025-02739-1","url":null,"abstract":"<p><strong>Background: </strong>Evidence from observational studies suggests an association between free cholesterol and gastric cancer. Immune cells play a crucial role in the tumor microenvironment of gastric cancer, and free cholesterol can influence immune cells in various ways, thereby impacting gastric cancer. The mechanisms by which free cholesterol regulates and activates the immune response to exert antitumor effects, as well as the causal relationship between free cholesterol and gastric cancer, remain unclear.</p><p><strong>Methods: </strong>We employed a two-sample Mendelian randomization (MR) approach to investigate the causal relationship between 233 metabolites and gastric cancer. Additionally, we validated our findings using data from GWAS databases of similar traits. Using publicly available genetic data, we analyzed the causal relationship between 731 types of immune cells and gastric cancer. Furthermore, we explored the mediating role of regulatory T cells in the causal relationship between free cholesterol and gastric cancer through multivariable Mendelian randomization. Finally, we validated our results using data from the TCGA database and single-cell sequencing data.</p><p><strong>Findings: </strong>We found a causal relationship between free cholesterol levels and gastric cancer (odds ratio [OR] = 0.89, confidence interval [CI] = 0.81-0.98, P < 0.05). We also observed a causal relationship between free cholesterol levels and regulatory T cells (odds ratio [OR] = 0.86, confidence interval [CI] = 0.75-0.98, P < 0.05), and between regulatory T cells and gastric cancer (odds ratio [OR] = 1.04, confidence interval [CI] = 1.01-1.07, P < 0.05). Additionally, our multivariable Mendelian randomization analysis indicated that regulatory T cells mediate the causal relationship between free cholesterol levels and gastric cancer. Furthermore, through single-cell sequencing analysis and data analysis from the TCGA database, we found that the expression of the free cholesterol uptake protein LDLR is negatively correlated with Treg infiltration, which further influences the occurrence and development of gastric cancer.</p><p><strong>Interpretation: </strong>Our analysis indicates a causal relationship between free cholesterol levels and gastric cancer, with regulatory T cells acting as mediators. Modulating free cholesterol levels to influence regulatory T cells may offer new insights and prospects for the prevention and treatment of gastric cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"864"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the \"inflammation-immunity-metabolism\" network in non-small cell lung cancer: a multi-omics analysis.","authors":"Jingqi Zhang, Liping Lin, Wenyuan Li, Jing Guo","doi":"10.1007/s12672-025-02692-z","DOIUrl":"10.1007/s12672-025-02692-z","url":null,"abstract":"<p><p>Lung cancer remains one of the leading causes of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of cases worldwide. NSCLC pathogenesis and progression are intricately linked to inflammatory stimuli, immune evasion, and metabolic reprogramming. In this study, the impact of inflammation, immunity, and metabolism on NSCLC was investigated by a Mendelian randomization analysis taking 91 inflammatory factors, 731 immune cells, and 1400 metabolites as exposures, and the FinnGen database NSCLC cohort (ncases = 5315, ncontrol = 314,193) was the outcome. A number of metabolites, inflammatory proteins, and immune cells were identified as potentially associated with NSCLC based on mendelian randomization analysis. Validation in the UK Biobank database lung cancer cohort (ncases = 2671, ncontrols = 372,016) further confirmed the inhibitory role of the metabolite N-acetyl-aspartyl-glutamate (NAAG) on lung cancer. Subsequently, single-cell and protein-protein interaction analyses identified inflammatory protein expression patterns in NSCLC, distribution ratios of immune cells in NSCLC. Subsequent multi-omics network analysis showed key interaction nodes between NAAG and inflammatory proteins. These findings enhance the understanding of the roles of inflammation, immunity, and metabolism in NSCLC occurrence and progression, offering potential targets and strategies for further research on its treatment and management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"847"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study.","authors":"Xujia Li, Lingli Huang, Yue Yan, Yuming Rong, Xuxian Chen, Mengge Gao, Jinsheng Huang","doi":"10.1007/s12672-025-02678-x","DOIUrl":"10.1007/s12672-025-02678-x","url":null,"abstract":"<p><strong>Background: </strong> The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms.</p><p><strong>Methods: </strong>A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms.</p><p><strong>Results: </strong>Height, obesity class 1, 2, and 3, overweight, waist-to-hip ratio, waist circumference, and serum uric acid were identified as factors associated with an augmented risk of colorectal neuroendocrine neoplasms (all p < 0.05). Conversely, a negative correlation was observed between fasting glucose and the risk of colorectal neuroendocrine neoplasms (p = 0.031). Platelet count exhibited a negative correlation with lung neuroendocrine neoplasms (p = 0.02). Moreover, the waist-to-hip ratio demonstrated a negative association with the risk of pancreatic neuroendocrine neoplasms. Atrial fibrillation, mean cell heamoglobin, and mean cell volume were positively associated with the risk of small intestine neuroendocrine neoplasms. In gastric neuroendocrine neoplasms, obesity class 1 and 2, overweight, and telomere length were implicated in their heightened risk. Following adjustment for multiple tests, obesity class 1 remained statistically significant to colorectal neuroendocrine neoplasms, and telomere length maintained significance in association with gastric neuroendocrine neoplasms. The outcomes of reverse MR suggested a bidirectional causal relationship between telomere length and gastric neuroendocrine neoplasms.</p><p><strong>Conclusion: </strong>This study provided genetic evidence for the causal relationships between potentially modifiable risk factors and the risk of five neuroendocrine neoplasms. Therapeutic approaches to these factors may provide a basis for preventing neuroendocrine neoplasms.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"841"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming and immune microenvironment profiling in clear cell renal cell carcinoma: implications for prognosis, targeted therapy, and drug resistance.","authors":"Xiao Zheng, Yongqiang Liu, Zixin Yang, Yanhua Tian","doi":"10.1007/s12672-025-02401-w","DOIUrl":"10.1007/s12672-025-02401-w","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer, distinguished by intricate interactions between metabolic reprogramming, immune microenvironment dynamics, and genetic mutations. In this detailed investigation, we analyzed the ccRCC cohort from The Cancer Genome Atlas (TCGA) alongside 81 metabolic signaling pathways from the KEGG database. By utilizing Gene Set Variation Analysis (GSVA), we performed hierarchical clustering of patients based on their metabolic pathway activity profiles, identifying three distinct clusters with notable differences in pathway activity and survival outcomes. Cluster 1 displayed high metabolic activity and more favorable survival outcomes, while Cluster 3 was characterized by low metabolic activity and poorer prognosis. Clinical comparisons revealed significant disparities in gender, histological stage, and survival status, with Cluster 3 exhibiting a higher proportion of patients at advanced stages and those who had passed away. Genetically, Cluster 1 showed the highest mutation burden, with prominent mutations in genes such as VHL and PBRM1. Biological process analysis indicated that pathways like organic carboxylic acid metabolism and ATP synthesis were upregulated in Cluster 1 but suppressed in Cluster 3. Machine learning models (GBM, CoxBoost, and LASSO regression) enabled the identification of four pivotal genes-BCAT1, IL4I1, ACADM, and ACADSB-which were subsequently used to construct a multifactorial Cox regression model. This model successfully stratified patients into high- and low-risk groups, correlating with marked differences in immune activities. The high-risk group showed elevated expression of chemokines, TNF, and HLA molecules. Drug sensitivity analysis suggested that AKT inhibitor III was more effective in the low-risk cohort, while Bortezomib might be more beneficial for high-risk patients. Additionally, a clinical prediction model integrating risk scores and clinical factors demonstrated strong predictive power for patient survival. Methylation profiling of the core genes via the UALCAN platform revealed distinct epigenetic signatures in ccRCC, providing deeper insight into the disease's molecular mechanisms. This study contributes to a more comprehensive understanding of ccRCC and proposes valuable directions for personalized treatment strategies and enhanced patient management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"850"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of arecoline-induced oral cancer: a network toxicology and molecular docking techniques integrated analysis.","authors":"Linghan Leng, Xin Wang, Hao Wang, Yingchun Hu, Yaxing Deng, Chenglin Wang","doi":"10.1007/s12672-025-02659-0","DOIUrl":"10.1007/s12672-025-02659-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The IARC classified betel nut as Group 1 carcinogen (2004) and arecoline as Group 2B carcinogen (2020), with approximately one-third of global oral cancer cases attributed to smokeless tobacco or betel nut consumption. While current evidence establishes an association between arecoline and oral cancer, the underlying molecular mechanisms remain complex and poorly elucidated. This study employs network toxicology integrated with molecular docking techniques to systematically investigate the potential molecular pathogenesis of arecoline-induced oral cancer, aiming to provide novel insights for targeted therapeutic strategies. The SMILES structure of arecoline was retrieved from PubChem for foundational data preparation. Toxicity profiling was conducted using ProTox-3.0 and ADMETlab databases. Potential targets of arecoline were identified via STITCH and SwissTargetPrediction. Oral cancer-related targets were collated from GeneCards, OMIM, and TTD. Intersection analysis between arecoline targets and oral cancer-associated targets was performed to identify shared targets, which were further utilized to construct compound-target regulatory network and subjected to PPI, GO, and KEGG analyses. Core targets driving oral cancer were screened using the cytoHubba plugin. Then, the correlation between core targets and immune cell infiltration in oral cancer was explored, and molecular docking validated the binding affinity of arecoline to core targets. Finally, Gromacs 2022.3 software was used to simulate the molecular dynamics of the complexes obtained by molecular docking for 100 ns. Using the STITCH and SwissTargetPrediction databases, a total of 46 potential targets of arecoline were identified. Concurrently, 2,375 oral cancer-related targets were retrieved from GeneCards, OMIM, and TTD. Intersection analysis of these two target sets yielded 26 overlapping targets. PPI analysis revealed that TP53, IL6, SNAI1, and CASP3 occupied central positions in the network, exhibiting extensive interactions with other target proteins. Enrichment analysis comprehensively elucidated the molecular functions, biological processes, cellular components, and associated pathways of these overlapping targets. Further screening using Cytoscape software identified four core targets: TP53, TNF, IL6, and CASP3. Immune infiltration analysis indicated that the expression levels of TP53, TNF, IL6, and CASP3 in oral cancer tissues were positively correlated with the infiltration levels of immune cells, including CD8 + T cells, Th1 cells, NK cells, and macrophages. Molecular docking experiments demonstrated strong binding activities between arecoline and TP53, IL6, and CASP3, while TNF also exhibited moderate binding affinity. Dynamic simulation further verified the stable binding of arecoline to TP53, TNF, IL6 and CASP3. Arecoline may induce oral cancer by acting on core targets including TP53, TNF, IL6, and CASP3, which interfere with normal cellular growth regulation, inflamm","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"842"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchronous triple primary colorectal cancer: a rare case report from a rural tibetan population.","authors":"Qing Zhou, Jin-Ke Kang, Yong-Fa Zhi, Ming-Jie Ma, Xiao-de Ren, Zheng-Ning Gan, Jie Niu","doi":"10.1007/s12672-025-02647-4","DOIUrl":"10.1007/s12672-025-02647-4","url":null,"abstract":"<p><p>Synchronous multiple colorectal cancers (SMCRC) are rare and defined as distinct malignant tumors occurring simultaneously in the colon and rectum without evidence of metastasis from one tumor to another. This case report presents a 69 year-old Tibetan male admitted with acute abdominal pain, abdominal distension, nausea, and vomiting. Imaging studies and colonoscopy revealed synchronous cancers in the rectum, sigmoid colon, and transverse colon, all pathologically confirmed as moderately differentiated adenocarcinomas. The patient underwent a multisegment colectomy with complete resection of all tumors. Postoperative recovery was uneventful, and no recurrence was reported during follow-up. This case underscores the importance of thorough diagnostic and surgical strategies for SMCRC, particularly in emergency presentations where limited diagnostic modalities may pose challenges.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"839"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy-related second malignant neoplasms on top of neuroblastoma: frequency, types and risk factors.","authors":"Mohamed Fawzy, Nihal Abdelfattah, Menna Alaa, Inas Mohsen, Sonya Soliman, Sherine Salem, Wael Zekri, Omar Arafah","doi":"10.1007/s12672-025-02661-6","DOIUrl":"10.1007/s12672-025-02661-6","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of the study was to evaluate the long-term effect of multi-modal, risk-based treatment protocols on the development of treatment-related secondary malignant neoplasm (SMN) in patients during or after treatment of Neuroblastoma.</p><p><strong>Material and methods: </strong>This retrospective study included all patients with neuroblastoma treated at Children's Cancer Hospital-Egypt from July 2007 to December 2022.</p><p><strong>Results: </strong>24 out of 2290 patients (1%) received risk-tailored multimodal treatment protocols suffered from either hematological (21/24) or solid (3/24) treatment-related SMN during or after treatment of their primary neuroblastoma disease. Age at neuroblastoma diagnosis ranged from 6 mo to 9.5 y (median age: 2 y) with male to female ratio of 1.2:1. Time to development of hematological treatment-related SMN was 14 mo to 8.3 y (mean: 3.7 y) versus 5.5-9.2 y (mean: 7.6 y) for solid treatment-related SMN. High cummulative doses of ifosfamide, cyclophosphamide, and etoposide were most frequently encountered among study patients.</p><p><strong>Conclusions: </strong>Patients with neuroblastoma are at more risk of developing hematological than solid treatment-related SMN after relatively longer duration for latter compared to former tumor subtypes. High-risk treatment regimens and higher cumulative doses of alkylating agents and Topoisomerase-II inhibitors are likely associated with increased risk of treatment-related SMN.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"851"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine methylation patterns in LUAD: defining prognostic subtypes and relevance to immunotherapy.","authors":"Qianyun Shen, Yijie Yang, Maoying Guan, Hegen Li","doi":"10.1007/s12672-025-02549-5","DOIUrl":"10.1007/s12672-025-02549-5","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the leading cause of cancer-related death worldwide, with lung adenocarcinoma (LUAD) being the most common subtype. Arginine methylation, driven by protein arginine methyltransferases (PRMTs) has been connected to cancer biology, particularly in modulating cancer immunity. Thus, developing a PRMTs-related prognostic model might help create more personalized treatment plans for LUAD patients.</p><p><strong>Methods: </strong>We conducted an integrative analysis using multi-omics data from LUAD samples within the TCGA and GEO database, focusing on the expression profiles of nine PRMTs. Employing machine learning, we developed a PRMTs-related prognostic model, to evaluate the clinical and immunological features of LUAD patients.</p><p><strong>Results: </strong>We stratified 440 LUAD patients into two distinct clusters (PRMTCluster A and B), which exhibited significant differences in prognosis and immune infiltration. The PRMTs-related prognostic model, incorporating genes CLIC6, CLDN2, and BPIFB1, was significantly associated with patient outcomes and immune signature. RT-qPCR showed that the expression level of PRMT1, PRMT3, PRMT4, PRMT5, and PRMT7 was significantly upregulated in H1975 and A549 cells than in BEAS 2B cells.</p><p><strong>Conclusion: </strong>We developed a PRMTs-related prognostic model for assessing prognosis and immunotherapy responses in LUAD. This model was vital for developing more personalized and effective treatment plans for LUAD patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"853"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization analysis reveals the potential of the IKZF1 gene as a therapeutic target in colorectal cancer.","authors":"Junzuo Lin, Qian Xu, Zhengfei Zhao","doi":"10.1007/s12672-025-02683-0","DOIUrl":"10.1007/s12672-025-02683-0","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is a global health burden, highlighting the urgent need for the discovery of new biomarkers and therapeutic targets. This study integrates genetic epidemiology methods, such as Mendelian randomization (MR), with GWAS data to predict treatment efficacy and identify novel CRC therapeutic targets.</p><p><strong>Methods: </strong>We utilized cis-eQTL data from the eQTLGen consortium and CRC GWAS data from the IEU Open GWAS database. MR analysis was conducted via the R package TwoSampleMR. Bayesian colocalization analysis was applied to identify shared genetic effects between CRC risk factors and potential therapeutic targets. Phenome-wide association study (PheWAS), protein-protein interaction (PPI) network construction, and enrichment analyses were performed to elucidate the functional profiles of the targets. Molecular docking and dynamics simulations were employed to evaluate the therapeutic potential of the identified targets.</p><p><strong>Results: </strong>MR analysis identified 60 genes associated with CRC risk. Our analysis identified IKZF1 as a significant therapeutic target through colocalization analysis. The PheWAS results revealed no significant genomic correlations for IKZF1, suggesting its potential as a specific therapeutic target. PPI and enrichment analyses highlighted the role of IKZF1 in epigenetic regulation and transcriptional control. Molecular docking and dynamics simulations confirmed the strong binding affinities of potential drugs with IKZF1.</p><p><strong>Conclusion: </strong>This study identified IKZF1 as a promising therapeutic target for CRC through MR and colocalization analyses. The target's association with immune modulation and epigenetic mechanisms, supported by molecular docking and dynamics simulations, positions IKZF1 as a key player in advancing precision CRC therapies, warranting further clinical investigation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"838"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the molecular mechanism of UBA52 and BARD1 regulating hepatocellular carcinoma through the PI3 K/AKT signaling pathway.","authors":"Chenrui Yang, Yanzhong Zhang, Yajuan Liu, Xiaoyong Wu, Fangyuan Sun","doi":"10.1007/s12672-025-02600-5","DOIUrl":"10.1007/s12672-025-02600-5","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally, with its development closely related to complex molecular mechanisms such as gene mutations and abnormal signaling pathways. However, the specific roles of many key genes remain unclear. UBA52 and BARD1 are important genes associated with protein degradation, DNA repair, and cell cycle regulation, but their mechanisms in liver cancer are not well understood.</p><p><strong>Methods: </strong>This study integrated HCC datasets (GSE135631, GSE184733, GSE202853) from the gene expression omnibus (GEO) database to screen for differentially expressed genes (DEGs), perform functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), construct protein-protein interaction (PPI) networks, and conduct survival analysis. Western Blot (WB) and RT-qPCR experiments were used to verify the expression of UBA52 and BARD1 in liver cancer cells and their association with the PI3K/AKT signaling pathway.</p><p><strong>Results: </strong>Bioinformatics analysis identified UBA52 and BARD1 as core genes, showing high expression in HCC tissues and correlation with poor prognosis. Western Blot and RT-qPCR results further confirmed the high expression of UBA52 and BARD1 in HCC cell lines (HepG2 and Hep3b). PI3K inhibitors significantly downregulated the expression of UBA52 and BARD1, restored the levels of apoptosis-related factors (Fas, BAX, Caspase-3), and inhibited the expression of cell cycle-related proteins (Cyclin-D1, c-Myc). These findings suggest that UBA52 and BARD1 may regulate HCC cell proliferation, apoptosis, and metastasis through the PI3K/AKT signaling pathway. Furthermore, the molecular mechanism of hepatocellular carcinoma can be modulated by knocking out BARD1 or UBA52.</p><p><strong>Conclusion: </strong>UBA52 and BARD1 are highly expressed in HCC, and their abnormal expression may promote the occurrence and development of liver cancer by regulating the PI3K/AKT signaling pathway and mechanisms related to apoptosis and cell cycle. The high expression of UBA52 and BARD1 is closely associated with poor prognosis, indicating their potential value as early diagnostic and targeted therapeutic biomarkers for HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"840"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}