Discover. Oncology最新文献

{"title":"Multi-omics insights into the roles of CCNB1, PLK1, and HPSE in breast cancer progression: implications for prognosis and immunotherapy.","authors":"Qisheng Su, Leiming Fang, Chaofan Li, Liang Yue, Zhimin Yun, Huiqiang Zhang, Qi Liu, Ruilin Ma, Pengfei Zhong, He Liu, Zhangrong Lou, Zhi Chen, Yingxia Tan, Xiaopeng Hao, Chengjun Wu","doi":"10.1007/s12672-025-02282-z","DOIUrl":"10.1007/s12672-025-02282-z","url":null,"abstract":"<p><strong>Background: </strong>This study examines the roles of Cyclin B1 (CCNB1), Polo-Like Kinase 1 (PLK1), and Heparanase (HPSE) in breast cancer progression using a multi-omics approach. These genes are known for their involvement in various cancer-related processes, but their precise contributions to breast cancer remain unclear.</p><p><strong>Methods: </strong>We employed an integrative analysis combining transcriptomics, proteomics, DNA methylation profiling, immune infiltration analysis, and single-cell RNA sequencing to investigate the expression patterns, regulatory mechanisms, and functional impacts of CCNB1, PLK1, and HPSE in breast cancer. Functional assays using si-RNA knockdown of CCNB1 and PLK1 were performed to assess their roles in cell proliferation.</p><p><strong>Results: </strong>CCNB1, PLK1, and HPSE are upregulated in breast tumors at the mRNA and protein levels. CCNB1 and PLK1 promote tumor growth and metastasis, while HPSE is linked to immune pathways. DNA methylation in BRCA correlates with prognosis, with PLK1 alterations protective for recurrence-free survival. High expression of these genes worsens prognosis, with CCNB1 as a risk factor for overall survival. Immune infiltration analysis associates these genes with tumor-infiltrating immune cells, highlighting HPSE's immunotherapeutic potential. Single-cell RNA sequencing confirms CCNB1 and PLK1 drive malignant proliferation and an immunosuppressive environment. Functional assays demonstrated that silencing CCNB1 and PLK1 significantly reduced breast cancer cell proliferation, indicating regulatory interactions among PLK1, CCNB1, and MKI67.</p><p><strong>Conclusions: </strong>This study provides evidence that CCNB1, PLK1, and HPSE are key players in breast cancer progression and potential biomarkers for prognosis. Furthermore, their roles in immune regulation suggest they could be promising targets for immunotherapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"471"},"PeriodicalIF":2.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788006","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":"Isorhamnetin inhibits cholangiocarcinoma proliferation and metastasis via PI3K/AKT signaling pathway.","authors":"Zhiguo Tan, Jie Liu, Min Hou, Jia Zhou, Yu Chen, Xu Chen, Yufang Leng","doi":"10.1007/s12672-025-02217-8","DOIUrl":"10.1007/s12672-025-02217-8","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma (CCA), which is a malignant tumor originating from the epithelial cells of the bile ducts, has witnessed an increasing incidence year by year. Owing to the dearth of effective treatments, the prognosis for CCA is rather poor. Isorhamnetin is known to possess anti-tumor, anti-inflammatory and oxidative stress modulating effects; however, its role in CCA remains unclear.</p><p><strong>Methods: </strong>Firstly, we screened the core targets and pathways of isorhamnetin for the treatment of CCA through a network pharmacology approach. Subsequently, we verified via molecular docking that the core targets could dock stably with isorhamnetin. Finally, we verified the inhibitory effect of isorhamnetin on the malignant biological behavior of CCA in vitro and in vivo experiments.</p><p><strong>Results: </strong>Based on the network pharmacology analysis, we came to the conclusion that AKT1 might be a core target of isorhamnetin in the treatment of CCA. Molecular docking indicated that AKT1 was capable of binding stably to isorhamnetin. Subsequently, In vitro experiments demonstrated that isorhamnetin was able to suppress the proliferation and metastasis of CCA cells, and AKT1 played a pivotal role in this process. Mechanistically speaking, isorhamnetin exerts its inhibitory effect on tumor growth via the PI3K/AKT signaling pathway.</p><p><strong>Conclusions: </strong>Our study demonstrated for the first time that isorhamnetin can inhibit the progression of CCA through PI3K/AKT, and that AKT1 may be a target of isorhamnetin for the treatment of CCA.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"469"},"PeriodicalIF":2.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788004","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":"Flavonoid GL-V9 suppresses development of human hepatocellular cancer cells by inhibiting Wnt/β-Cantenin signaling pathway.","authors":"Ye Gu, Qiaoxian He, Lu Xie, Fangfang Chen, Hangbin Jin, Lilan Lou, Xiaofeng Zhang","doi":"10.1007/s12672-025-01845-4","DOIUrl":"10.1007/s12672-025-01845-4","url":null,"abstract":"<p><p>Distant metastasis and post-operative recurrence of tumours are the main causes of death in patients with hepatocellular carcinoma (HCC). In recent years, flavonoids have been found to achieve effective anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis, inhibiting cancer cell invasion and metastasis and neovascularization. GL-V9 is a newly synthesized flavonoid that has been demonstrated anticancer effects in a variety of tumors, but its anticancer effects in HCC and its related mechanisms are still unclear. In this study, we investigated the anti-proliferative, anti-invasive and anti-migratory activities of GL-V9 in HCC cells by MTT method cell proliferation assay, plate cloning assay, transwell invasion assay and cell scratching assay. Based on the results, we found that GL-V9 inhibits the EMT process through a pathway that inhibits Wnt/β-Cantenin pathway signaling, thereby reducing the proliferation, migration and invasion ability of HCC cells. Therefore, GL-V9 may be a novel potential therapeutic agent to inhibit HCC cell metastasis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"462"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788001","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":"Constructing a prognostic model based on MPT-related genes and investigate the characteristics of immune infiltration in bladder cancer.","authors":"Lei Yang, Zhiqiang Zhang, Mengfan Xu, Muhan Shang, Haibing Wang, Zhiqi Liu","doi":"10.1007/s12672-025-02222-x","DOIUrl":"10.1007/s12672-025-02222-x","url":null,"abstract":"<p><strong>Purpose: </strong>Exploring the expression of Mitochondrial Permeability Transition Dependent Necrosis lncRNA in bladder cancer and elucidate their precise function within the tumor microenvironment and impact on prognosis.</p><p><strong>Methods: </strong>We employed a comprehensive bioinformatics approach to investigate the function and influence of lncRNA in bladder cancer. Gene expression data, clinical data, and mutation data of bladder cancer are obtained from TCGA database.</p><p><strong>Results: </strong>We developed a new prognostic model incorporating 6 lncRNAs. The predictive efficacy of this model for bladder cancer prognosis was validated. Furthermore, we investigated the influence of model on the tumor microenvironment and drug sensitivity.</p><p><strong>Conclusion: </strong>This study presents a novel prognostic framework for bladder cancer that holds great potential for enhancing prognostic prediction accuracy and optimizing treatment strategies for patients with this disease.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"460"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779410","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":"Identification of necroptosis & mitophagy-related key genes and their prognostic value in colorectal cancer.","authors":"Xiuling Zhang, Li Meng, Tingjian Zu, Qian Zhou","doi":"10.1007/s12672-025-02221-y","DOIUrl":"10.1007/s12672-025-02221-y","url":null,"abstract":"<p><strong>Background: </strong>Our study aimed to elucidate the potential necroptotic&mitophagy-related key genes in colorectal cancer (COAD) by bioinformatics analysis and identify their prognostic value in COAD.</p><p><strong>Methods: </strong>Firstly, we integrated the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets to identify necroptosis & mitophagy-related differentially expressed genes (N&MRDEGs) in COAD using \"TCGAbiolinks\" and \"GEOquery\" packages. Secondly, the obtained data were used for differential expression analysis using the \"limma\" package, and further functional enrichment analysis using the \"clusterProfiler\" package. Then, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were utilized to explore pathway associations of the N&MRDEGs. Thirdly, the predictive model was developed utilizing LASSO (Least absolute shrinkage and selection regression) regression implemented through the \"glmnet\" package and validated via Kaplan-Meier analysis. Finally, we validated the function of the key genes by receiver operating characteristic (ROC) curve analysis, multivariate cox proportional hazards model and COAD cell lines.</p><p><strong>Results: </strong>There is a strong association between the 4 key genes (UCHL1, HSPA1A, MAPK8, and PLEC) of COAD and the necroptotic&mitophagy, which were found to be lowly mRNA level in COAD cell lines. Among them, PLEC exhibited a pronounced contribution to the utility of the model in the TCGA database and UCHL1 has excellent diagnostic potential with an area under the curve (AUC) greater than 0.9.</p><p><strong>Conclusions: </strong>The perspective of bioinformatics analysis provides robust evidence suggested that UCHL1, HSPA1A, MAPK8, and PLEC genes are the prognostic biomarkers of COAD, the predictive model established herein provides a novel tool for risk stratification in clinical practice and serves as a foundation for further investigation into its underlying molecular mechanisms.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"461"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779494","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":"The application of mendelian randomization in cancer research: a bibliometric analysis.","authors":"Zhongtao Bai, Genlong Zhang","doi":"10.1007/s12672-025-02226-7","DOIUrl":"10.1007/s12672-025-02226-7","url":null,"abstract":"<p><p>Cancer is a major public health and economic issue faced globally today, significantly affecting human health and life. Due to various constraints, exploring the causal relationship between risk factors and cancer is challenging and not exactly accurate. The advent of Mendelian randomization (MR) effectively addresses these issues, providing new avenues for exploring causal relationships. We downloaded literature related to the application of MR in cancer from the Web of Science Core Collection (WoSCC) from 2005 to October 21, 2024, limiting the document type to articles and the language to English, resulting in a total of 2058 articles. We downloaded them in plain text format and extracted information on countries, authors, institutions, keywords, journals, citation counts, and publication dates, utilizing VOSviewer, CiteSpace, and R language for bibliometric analysis. From 2005 to 2024, the number of publications on the application of MR in cancer has shown a growth trend. China was the most productive country (1305); the University of Bristol was the most prolific institution (213); Smith, George Davey published the most articles in this field (59) with a total citation count of 5344; the most prolific journal in this field is Scientific Reports (71). Chronic diseases and cancer, inflammation and cancer, and sex hormones and cancer are three hot topics in the current research on the application of MR in cancer. In the future, optimizing statistical methods, standardizing research processes, collecting data from a broader range of populations, expanding data scale, and integrating other research methods to enhance research quality will be the development trends of MR in cancer research. In summary, this study employed bibliometric methods to comprehensively analyze the literature on the application of MR in cancer over the past 20 years, evaluating the historical development, current applications, research hotspots, and future trends of MR in the field of cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"463"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788012","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":"Prediction of potential targets of aloe-emodin in the treatment of hepatocellular carcinoma using network pharmacology combined with bioinformatics.","authors":"Jinlong Wei, Haosong Chen, Maoqi Xu, Zhenglin Zhang, Jin Wang, Wen Jiang, Weiguo Zhou, Maoming Xiong","doi":"10.1007/s12672-025-02215-w","DOIUrl":"10.1007/s12672-025-02215-w","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is one of the most common and malignant tumors worldwide. Although aloe-emodin (AE), a pure natural drug, can effectively kill hepatocellular carcinoma cells, its internal molecular mechanism has not been fully elucidated. In this study, the anti-hepatocellular carcinoma targets of AE were predicted using network pharmacology and bioinformatics.</p><p><strong>Methods: </strong>The differentially expressed genes between hepatocellular carcinoma and normal tissues were first identified and then further intersected with the potential pharmacological target genes of AE for subsequent analysis. Moreover, the potential targets of AE were enriched and analyzed to identify potential downstream pathways. The binding ability and interaction between the above drug targets and AE were analyzed by molecular docking. The prognostic model of hepatocellular carcinoma was subsequently constructed via univariate Cox regression analysis, LASSO regression analysis and multivariate Cox regression analysis. Finally, the potential targets that can stably bind to AE were further screened through molecular dynamics simulation. Finally, we validated the potential utility of AE in treating hepatocellular carcinoma through in vitro experiments.</p><p><strong>Results: </strong>After 90 target genes related to AE were crossed with hepatocellular carcinoma differential genes, 13 cross genes were obtained. The above 13 genes might act on hepatocellular carcinoma through the following pathways: p53 signaling pathway, cell cycle, cellular sense, mismatch repair, apoptosis-multiple specifications, base example repair and DNA replication. Molecular docking revealed that the combination of the BAX, FASN, CDK1, PCNA, CLIC1, VWF, RAN, FOXM1, TGM3, CANT1, and NSMCE2 proteins with AE was relatively stable. A 4-gene prognostic model was further constructed. The area under the curve (AUC) values of the 1-year, 3-year and 5-year survival rates from the ROC curve were 0.809, 0.673 and 0.641, respectively. Molecular dynamics analysis revealed that CDK1 and PCNA were the most stable binding targets among the above proteins. CCK8 and wound healing assays revealed that AE inhibited the proliferation and migration of hepatocellular carcinoma cells at increasing concentrations. Western blot experiments revealed that AE achieved therapeutic effects on hepatocellular carcinoma by promoting apoptosis of hepatocellular carcinoma cells.</p><p><strong>Conclusions: </strong>Based on network pharmacology, bioinformatics, molecular dynamics simulation, and in vitro experimental verification, we found that AE achieved a therapeutic effect on hepatocellular carcinoma by promoting apoptosis of hepatocellular carcinoma cells.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"464"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788007","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":"Radiotherapy-immunity lncRNA model predicts lung adenocarcinoma prognosis and treatment outcome and distinguishes between hot and cold tumors.","authors":"Lingfan Xiong, Jing Guo, Jingjun Lv, Wenhao Guo, Tingting Qiu","doi":"10.1007/s12672-025-02184-0","DOIUrl":"10.1007/s12672-025-02184-0","url":null,"abstract":"<p><strong>Background: </strong>There are many prognostic markers for lung adenocarcinoma (LUAD). However, studies on the prognosis of LUAD by radiotherapy immune-related long noncoding RNAs (lncRNAs) are extremely rare.</p><p><strong>Methods: </strong>We have compiled 1121 radiotherapy susceptibility differential genes and 6195 immune-related genes. After that, we screened radiotherapy-immunity lncRNAs associated with proliferation by co-expression, univariate, least absolute shrinkage selection operator regression (LASSO), and multivariate analysis of variance. Finally, we constructed a prognostic model based on 6 lncRNAs, and verified the accuracy of the predictive model by ROC and C index. In addition, we used the constructed scoring model to analyze the model's association with the characteristics of immune cell infiltration, immune checkpoint and drug sensitivity. Finally, the whole sample was divided into 2 clusters to further distinguish hot and cold tumors.</p><p><strong>Results: </strong>We constructed a risk score model built on 6 prognostically relevant lncRNAs. Patients were categorized into high-risk and low-risk patients based on median scores in the Train group. We found that people in the high-risk group had a lower survival rate than those in the low-risk group. However, those in the high-risk group were more sensitive to chemotherapy, targeted drugs and also more sensitive to immunotherapy drugs. Based on the line graphs of T, N, Age, Stage and Risk, the corresponding scores can be summed up to visualize the survival rate of patients at 1, 3 and 5 years. Gene set enrichment analysis (GSEA) suggested that radiotherapy-immunity-related lncRNA might be related to pathways such as cell cycle, T cell receptor signaling pathway. It is noteworthy that in our study, cluster 1 was considered to be a hot tumor more sensitive to immunotherapy.</p><p><strong>Conclusion: </strong>In summary, we constructed a risk score model built on six radiosensitivity and immune-related lncRNAs, which is expected to be a potential predictive biomarker for radiosensitivity and LUAD prognosis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"455"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771428","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":"Identification of ferroptosis-related gene signatures as a novel prognostic model for clear cell renal cell carcinoma.","authors":"Xiaoxiao Du, Haoyuan Cao, Yu-Jie Zhou, Qingli Kong, Xulong Zhang","doi":"10.1007/s12672-025-02202-1","DOIUrl":"10.1007/s12672-025-02202-1","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC), a common type of renal cortical tumor, is the most prevalent subtype of renal malignancies within the urinary system and is associated with a low survival rate. Ferroptosis plays a crucial role in the process of renal carcinogenesis and holds potential for significant applications in patient prognosis. However, the clinical prognostic relevance of ferroptosis-related genes (FRGs) for ccRCC remains unclear. The identification of FRG signatures and the development of a novel prognostic model based on FRGs demonstrate important prognostic significance for ccRCC.</p><p><strong>Methods: </strong>Univariate cox screen was performed to screen for prognostic-related genes using ccRCC data from the The Cancer Genome Atlas (TCGA) database. And then an initial screen for prognostic genes was performed by taking intersections with the differential genes of the Gene Expression Omnibus (GEO) database datasets GSE213324 and GSE66271, as well as with the FRGs, and a multigene signature was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. Subsequently, the model was evaluated using Kaplan-Meier (KM) survival curve analysis, receiver operating characteristic (ROC), nomogram, and decision curve analysis (DCA). Differences in tumor microenvironment and immune function were analyzed by single-sample gene set enrichment analysis (ssGSEA) and immune infiltration in patients in the high- and low-risk groups. The tumor immune dysfunction and exclusion (TIDE) assessed the immune checkpoint inhibitor (ICI) susceptibility in patients. The Gene Set Enrichment Analysis (GSEA) was performed for pathway enrichment analysis. Patient mutation data were downloaded and tumor mutation burden (TMB) were compared between patients in the high- and low-risk groups.</p><p><strong>Results: </strong>ADACSB, DPEP1, KIF20A, MT1G, PVT1 and TIMP1 were utilized to establish a novel prognostic signature. The KM curve analysis revealed that patients in the high-risk group exhibited a poorer prognosis. Additionally, the ROC results demonstrated that the model displayed favorable prognostic accuracy. Independent prognostic analyses indicated that the FRGs model could serve as an independent prognostic indicator. Furthermore, calibration curve of the nomogram illustrated enhanced precision in predicting survival rates for patients at 1, 3 and 5 years. Analysis of mutation data unveiled higher tumor mutation load among patients in the high-risk group, which correlated with an increase in risk score.</p><p><strong>Conclusion: </strong>The FRGs model offers a novel approach for prognostic prediction of ccRCC patients and has the potential to provide personalized prognostic prediction and treatment for ccRCC patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"456"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771388","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":"Blocking lncRNA NOP14-AS1 overcomes 5-Fu resistance of colon cancer cells by modulating miR-30a-5p-LDHA-glucose metabolism pathway.","authors":"Ya-Nan Lu","doi":"10.1007/s12672-025-02156-4","DOIUrl":"10.1007/s12672-025-02156-4","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a malignant digestive tumor associated with high mortality rate. Currently, 5-Fu therapy is a frequently used treatment approach for CRC. Yet, acquirement of 5-Fu resistance ultimately leads to therapeutic failure in CRC patients. LncRNA NOP14-AS1 was upregulated in cancers, but its biological functions and mechanisms in 5-Fu resistant colorectal cancer remain elusive. We discovered that NOP14-AS1 was high-expressed in colorectal tumors and cancer cells. Silencing NOP14-AS1 sensitized CRC cells to 5-Fu. By creating a 5-Fu resistant CRC cell line (HT-29 5-Fu R) and observed that expression of NOP14-AS1 was remarkedly elevated in 5-Fu resistant cells compared to parental cells. Additionally, we found that miRNA-30a-5p was a target of NOP14-AS1 and directly affected its function. miR-30a-5p overexpression sensitized CRC cells to 5-Fu treatment and targeted the glycolysis key enzyme, LDHA. Rescue experiments showed that restoring LDHA in CRC cells which were overexpressing miR-30c-5p successfully overridden 5-Fu resistance. Importantly, restoring miR-30a-5p in NOP14-AS1-overexpressing cells effectively restored 5-Fu sensitivity in HT-29 5-Fu R cells by targeting the LDHA-mediated glucose metabolism. In summary, our results revealed that lncRNA NOP14-AS1 promotes 5-Fu resistance by mediating the miR-30a-5p-LDHA axis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"458"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779459","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}