Discover. Oncology最新文献

{"title":"Clinical value of the worst pattern of invasion in predicting extranodal extension in oral squamous cell carcinoma.","authors":"Mirai Higaki, Toshinori Ando, Fumitaka Obayashi, Nanako Ito, Suguru Hirota, Atsuko Hamada, Sachiko Yamasaki, Tomoaki Shintani, Koichi Koizumi, Souichi Yanamoto","doi":"10.1007/s12672-025-03058-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03058-1","url":null,"abstract":"<p><strong>Objective: </strong>Extranodal extension (ENE) is one of the major influencing factors for the oncological outcomes in oral squamous cell carcinoma (OSCC). We aimed to elucidate the clinical features predictive of ENE in OSCC.</p><p><strong>Materials and methods: </strong>We conducted a retrospective analysis of patients with OSCC who underwent neck dissection (ND) with a confirmed pN + status. Cases in which the histopathological evaluation was compromised by preoperative chemotherapy or radiotherapy were excluded. Histopathological evaluation of extent of ENE category and grading of worst pattern of invasion (WPOI) was compared for available cases.</p><p><strong>Results: </strong>Fifty-nine patients met the inclusion criteria for the study. Of these, 32/59 (54.2%) were ENE-positive. A higher incidence of ENE was observed in cases where ND was performed at a separate time from the primary tumor resection (odds ratio [OR] = 11.0, 95% confidence interval [95%CI] 2.23-54.5, P = 0.003). Additionally, a higher grade of WPOI (WPOI 4 or 5) was significantly associated with ENE occurrence (OR = 4.53, 95%CI 1.19-20.50, P = 0.026). A positive correlation between the WPOI grade and ENE extent was also identified (ρ = 0.412, P <.001).</p><p><strong>Conclusion: </strong>We demonstrated an association between WPOI and ENE in patients with OSCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1259"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism and biological pathway of high-expressed RAD51 in regulating cell adhesion and potentially affecting oral squamous cell carcinoma.","authors":"Yu-Xing Tang, Yu-Yan Pang, Yan Cui, Guo-Jiao Wu, Lin-Qing Huang, Chang-Zhan Zhou, Bin Li, Qi Li, Bang-Teng Chi, Rong-Quan He, Di-Yuan Qin, Jian-Di Li, Gang Chen, Dong-Ming Li, Yi-Wu Dang","doi":"10.1007/s12672-025-03085-y","DOIUrl":"https://doi.org/10.1007/s12672-025-03085-y","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral cavity, with over 70% of cases detected in advanced stages and a 5-year survival rate of 50%. RAD51, a crucial DNA repair molecule, has also been implicated in the regulation of cell adhesion. However, its multi-platform expression patterns and functional role in cell adhesion within the context of OSCC have not yet been comprehensively validated.</p><p><strong>Methods: </strong>Bulk RNA (RNA-seq and microarray), immunohistochemistry (IHC), and single-cell sequencing (scRNA-seq) were used to assess RAD51 expression and its clinical relevance in OSCC. CRISPR was used to knock out RAD51 and explore its effect on OSCC cell proliferation. Bulk RNA and scRNA-seq analyses were integrated to explore RAD51's molecular mechanisms, cellular communication, and metabolic pathways. Drug sensitivity analysis aimed to explore the relationship between RAD51 and drugs, while the target molecules of RAD51 transcription factors were identified.</p><p><strong>Results: </strong>In bulk RNA (1,006 OSCC samples), IHC (162 OSCC tissues), and scRNA-seq (9,693 malignant epithelial cells), RAD51 was comprehensively upregulated in OSCC. The proliferation of OSCC cells was inhibited due to knockout of RAD51. Bulk RNA and scRNA-seq indicated that RAD51 was associated with cell adhesion. High expression of RAD51 was associated with the MIF pathway in cell communication, with the TCA cycle metabolism being mainly regulated. The expression of RAD51 was associated with resistance to Erlotinib, Gefitinib, and Selumetinib. In the molecular network, RAD51 was demonstrated a targeting relationship with adhesion-related molecules like CD74, JUP and MIF.</p><p><strong>Conclusion: </strong>High expression of RAD51 may promote the advancement of OSCC by regulating the related mechanisms of cell adhesion.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1260"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of cholesterol homeostasis reveals prognostic subtypes and immune features in clear cell renal cell carcinoma.","authors":"Jian Zhu, Minghao Deng, Weizhuo Wang, Aijin Peng, Anli Zhu, Rongchao Yang, Zhenhua Jin, Dong Zhang, Xi Zhang","doi":"10.1007/s12672-025-03116-8","DOIUrl":"https://doi.org/10.1007/s12672-025-03116-8","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol is essential for tumor proliferation and progression. Cholesterol homeostasis has emerged as a key focus in cancer metabolism research. However, its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood.</p><p><strong>Methods: </strong>RNA-sequencing and clinical data of ccRCC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. The E-MTAB-1980 dataset served as an external validation cohort. Nonnegative Matrix Factorization was employed to construct the cholesterol homeostasis cluster. A cholesterol homeostasis signature (CHS) was constructed using the least absolute shrinkage and selection operator regression method to characterize the cholesterol metabolic status of ccRCC.</p><p><strong>Results: </strong>Two distinct molecular clusters associated with cholesterol homeostasis were identified, exhibiting divergent prognostic and immunological profiles. Analysis of immune cell infiltration revealed that Cluster C2 displayed immunosuppressive features, with enrichment of pro-tumor and immune-related pathways. The CHS was found to be predictive of both tumor immune status and clinical outcomes. Furthermore, we examined SREBF2, a key transcription factor in cholesterol regulation, and found that its high expression was associated with immune activation and favorable prognosis. Down-regulation of SREBF2 in ccRCC may lead to decreased cholesterol uptake and synthesis.</p><p><strong>Conclusion: </strong>Cholesterol homeostasis signature serves as a potential biomarker for prognosis, immune microenvironment status, and clinicopathological characteristics in ccRCC. Genes related to cholesterol homeostasis, such as SREBF2, may offer new therapeutic targets for immunomodulation in ccRCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1261"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals the potential role of estrogen in tuberous sclerosis complex related renal angiomyolipoma.","authors":"Yi Liu, Wenda Wang, Guoyang Zheng, Weifeng Xu, Zhan Wang, Xu Wang, Jiang Liu, Dongxu Qiu, Yanan Li, Yang Zhao, Yushi Zhang","doi":"10.1007/s12672-025-02909-1","DOIUrl":"https://doi.org/10.1007/s12672-025-02909-1","url":null,"abstract":"<p><strong>Purpose: </strong>Tuberous sclerosis complex (TSC) is a kind of rare genetic disorder caused by TSC1/TSC2 gene mutations and presented as angiomyolipoma (AML) in kidney. Previous studies have indicated the presence of estrogen-related heterogeneity in TSC, but this aspect has not been extensively explored.</p><p><strong>Methods: </strong>In the present study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the estrogen-related heterogeneity in TSC-AML. A total of two female and two male TSC-AML patients were included in this study.</p><p><strong>Results: </strong>Our results revealed the presence of various cell types within the TSC-AML tissue, including macrophages, endothelial cells, dendritic cells, neutrophils, B cells, fibroblasts, and tumor cells. Among the macrophage population, the immune-suppressive C1QC-Macro cells constituted the majority, and these cells were found to be more prevalent in female patients. AUCell analysis showed that estrogen-related pathways were significantly upregulated in C1QC-Macro cells in female patients compared to male patients. Furthermore, CellChat analysis demonstrated that tumor cells in female patients may regulate C1QC-Macro cells through the CXCL signaling pathway (CXCL12-CXCR4). In contrast, male patients exhibited enhanced interactions in stromal remodeling-related signaling pathways. Tumor cells were further categorized into TC1-TC6 subtypes. Notably, tumor cells with stem cell-like and EMT (epithelial-mesenchymal transition) characteristics were more common in male patients, whereas adipose-like, SMC-like, immune-suppressive, and fatty acid uptake-related tumor cells were more prevalent in female patients. Additionally, estrogen-related transcription factors (TFs), such as ESRRG, CREB1, CREB3L2, and CREB3L4, were activated in the stem cell-like tumor cells of female patients but not in those of male patients, suggesting that estrogen might play an important role in the pathogenesis of TSC-AML in females.</p><p><strong>Conclusion: </strong>Our findings indicate that estrogen regulates the formation of an immune-suppressive microenvironment and the development of stem cell-like tumors in female TSC-AML patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1255"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single‑cell RNA sequencing reveals TMEM71 as an immunomodulatory biomarker predicting immune checkpoint blockade response in breast cancer.","authors":"Boyang Li, Ruonan Lin, Yibo Hua, Binlin Ma, Yi Chen","doi":"10.1007/s12672-025-03068-z","DOIUrl":"https://doi.org/10.1007/s12672-025-03068-z","url":null,"abstract":"<p><strong>Background: </strong>TMEM71 is a poorly characterized transmembrane protein with unclear roles in cancer. This study aimed to explore its prognostic value, immune relevance, and therapeutic implications in breast cancer.</p><p><strong>Methods: </strong>We integrated transcriptomic, single-cell RNA-seq, immune infiltration and drug response data from TCGA, GTEx, GEO and public scRNA-seq datasets. Prognostic analysis, immune correlation (ssGSEA, CIBERSORT), functional enrichment (GO, KEGG, GSEA) and chemotherapy/immunotherapy sensitivity assessments were conducted.</p><p><strong>Results: </strong>TMEM71 was significantly downregulated in breast cancer and correlated with poor clinical outcomes. Single-cell analysis revealed its predominant expression in malignant and stromal cells. TMEM71 expression was associated with enhanced infiltration of immune cells, upregulation of immune checkpoints and enrichment of immune-related pathways. High TMEM71 expression predicted better response to immune checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4) and greater sensitivity to chemotherapeutics, including Gemcitabine, 5-fluorouracil and paclitaxel.</p><p><strong>Conclusion: </strong>TMEM71 is a novel immune-related gene with potential as a prognostic biomarker and predictor of therapy response in breast cancer. These findings offer new insights into the immunological role of TMEM71 and support its potential utility in guiding personalized treatment strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1256"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective targeting of the AKT1 (E17K) mutation: advances in precision oncology and therapeutic design.","authors":"Xiaoyan Chen, Danfeng Zhang, Jiapeng Xue, Zhi Li","doi":"10.1007/s12672-025-03083-0","DOIUrl":"https://doi.org/10.1007/s12672-025-03083-0","url":null,"abstract":"<p><p>The AKT1 (E17K) mutation, associated with unfavourable outcomes in solid tumours, promotes cancer proliferation and persistence. A recent study by Gregory et al. discovered a reversible covalent inhibitor targeting this mutation, exhibiting significant anti-tumor action with little effects on normal cells. This advancement provides a targeted therapeutic approach for AKT-mutant malignancies and informs further inhibitor research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1257"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical pathological methods for reliable diagnosis of secretory carcinomas of the salivary gland.","authors":"Ryo Kawaura, Tomohiko Ishikawa, Hirofumi Shibata, Masashi Kuroki, Kazuhiro Kobayashi, Yuki Hanamatsu, Tatsuhiko Miyazaki, Hiroyuki Tomita, Takuma Ishihara, Hajime Usubuchi, Yayoi Aoyama, Yukinori Asada, Takayuki Imai, Akira Ohkoshi, Akira Hara, Yukio Katori, Toru Furukawa, Takenori Ogawa","doi":"10.1007/s12672-025-03072-3","DOIUrl":"https://doi.org/10.1007/s12672-025-03072-3","url":null,"abstract":"<p><p>Secretory carcinomas (SCs) of the salivary gland have recently been recognized as low-grade, malignant tumors. Before this designation, most SCs were diagnosed as variants of acinic cell carcinomas (AciCCs). SCs harbor the t(12;15)(p13;q25) translocation that generates an oncogenic fusion gene, ETS variant transcription factor 6/Neurotrophic tyrosine receptor kinase(ETV6::NTRK3). However, detecting fusion genes in a clinical setting is time-consuming and costly. In this study, we examined 31 cases previously diagnosed as AciCC and SC using pathological analyses with detection of fusion genes using ETV6 break-apart fluorescence in-situ hybridization and reverse transcription-polymerase chain reaction. After re-analysis, we found that these 31 cases actually comprised 21 SCs and 10 AciCCs. We examined the diagnostic utility of immunohistochemistry by comparing results with the fusion gene, Pan-Trk, which despite having recently been reported as effective for diagnosis of SC, was not universally accurate. However, combining mammaglobin and S-100 could be particularly useful in diagnosing SC. This practical method will contribute to accurate diagnosis of SCs, while saving time in daily clinical practice.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1254"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of JPT1 in hepatocellular carcinoma: tumor progression, microtubule dynamics regulation, and potential mechanisms within the immune microenvironment.","authors":"Yipin Lu, Peng Xu, Sha Li, Jie Yao","doi":"10.1007/s12672-025-03066-1","DOIUrl":"https://doi.org/10.1007/s12672-025-03066-1","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy worldwide, with its progression and metastasis significantly impacting patient prognosis. JPT1 (Jupiter microtubule-associated homolog 1), a novel microtubule-associated protein, has been implicated in regulating cytoskeletal stability, microtubule dynamics, and the immune microenvironment, thereby potentially driving HCC development and progression. However, the precise role and underlying mechanisms of JPT1 in HCC remain poorly understood.</p><p><strong>Methods: </strong>This study integrated data from TCGA-LIHC and GEO (GSE14520) databases to systematically investigate the expression profile of JPT1 and its association with clinicopathological features and prognosis in HCC patients. A pan-cancer analysis was performed to evaluate JPT1 expression patterns and prognostic value across multiple cancer types. Differentially expressed gene (DEG) analysis, functional enrichment analysis (GSEA and KEGG), and spatial transcriptomics were utilized to explore the biological functions and mechanisms of JPT1 in tumor biology. Kaplan-Meier survival analysis and Cox proportional hazard models were employed to assess the prognostic potential of JPT1, while a nomogram was constructed to predict 1-, 3-, and 5-year survival rates in HCC patients.</p><p><strong>Results: </strong>JPT1 was significantly overexpressed in HCC tissues, and high JPT1 expression was strongly associated with poor prognosis. The ROC analysis demonstrated that JPT1 expression had high diagnostic accuracy for HCC, with AUC values of 0.931 and 0.948 in the TCGA and GEO cohorts, respectively. Functional enrichment analysis revealed that JPT1-associated genes were enriched in pathways related to cell cycle regulation, DNA replication, and organic acid metabolism. GSVA further indicated that the high JPT1 expression group was significantly enriched in hallmark pathways such as hypoxia response, hormone response, and KRAS signaling. Spatial transcriptomics analysis showed that JPT1 was predominantly localized in low malignancy tumor regions and positively correlated with immune cells, including CD4 + T cells, CD8 + T cells, and macrophages. Additionally, high JPT1 expression was associated with an increased mutation frequency of TP53 and CTNNB1.</p><p><strong>Conclusions: </strong>JPT1 plays a pivotal role in HCC progression, with its overexpression strongly linked to tumor advancement and poor prognosis. JPT1 likely contributes to the malignant evolution of HCC by modulating tumor metabolism, cell cycle regulation, and the immune microenvironment. This study provides a comprehensive insight into the role of JPT1 in HCC and establishes a theoretical foundation for its potential as a molecular biomarker and therapeutic target.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1258"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia.","authors":"Hong Zhang, Linlin Yang, Yukexin Liu, Dongju Wang, Liming Shi, Changyu Tian","doi":"10.1007/s12672-025-02383-9","DOIUrl":"10.1007/s12672-025-02383-9","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a devastating form of blood cancer characterized by uncontrolled growth and impaired maturation of myeloid precursor cells in the bone marrow. Despite advancements in treatment strategies, the prognosis for AML patients remains poor. The NLRP3 inflammasome, a multi-protein complex involved in innate immunity and inflammation, has been implicated in various diseases; however, its role in AML development and progression is not well understood. In this study, we analyzed genomic, bulk-, and single-cell transcriptomic data to assess the contribution of NLRP3 inflammasome genes to AML. Results suggested that 28 NLRP3 inflammasome genes with clinical implications were dysregulated in AML. Notably, we identified seven prognosis-related genes: CASP1, CPTP, MEFV, NFKB2, PANX1, PYCARD, and SIRT2. To further investigate the functional relevance of NLRP3 inflammasome genes, we developed an NLRP3 score (Nscore) based on the expression levels of these seven genes. We identified four dysregulated gene clusters that distinguished high- and low-Nscore groups, enabling the identification of two distinct AML subtypes, with subtype 2 exhibiting worse overall survival than subtype 1. Additionally, using a network-based approach, we identified 62 NLRP3 inflammasome-related genes and constructed a risk score model with COL2A1, ITGB2, and SRC genes, providing a comprehensive assessment of patient risk stratification. We revealed a positive correlation between the Nscore and macrophage M1, suggesting potential drug response mechanisms. Based on the identified AML subtypes and their distinct mutational landscapes, we predicted potential treatment options, with Paclitaxel, Afuresertib, and Mitoxantrone emerging as potential therapeutic agents for the AML subtypes.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"649"},"PeriodicalIF":2.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539384","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":"Mitochondrial pyruvate carrier inhibits tumor growth by Bmi1 ubiquitination in renal cell carcinoma progression.","authors":"Dan Jian, Nana Hu, Rong He, Le He, He Xiao, Xingqiao Peng, Yang Peng, Yuxin Yang, Xiaoyan Dai, Dong Wang, Yan Feng, Nan Dai, Qian Chen","doi":"10.1007/s12672-025-03053-6","DOIUrl":"10.1007/s12672-025-03053-6","url":null,"abstract":"<p><p>Mitochondrial pyruvate carrier (MPC), composed of MPC1 and MPC2, plays a pivotal role in regulating cancer metabolism. While previous studies have implicated MPC1 in tumor progression, the specific function of MPC2 in renal cell carcinoma (RCC) remains largely unclear. In this study, we found that reduced MPC2 expression was significantly associated with advanced TNM stage and poor patient prognosis. Functional assays demonstrated that MPC2 suppresses RCC cell proliferation both in vitro and in vivo. Additionally, concurrent low expression of MPC2 and MPC1 was correlated with significantly shorter overall survival, suggesting their combined prognostic value. Gene set enrichment analysis indicated that both MPC1 and MPC2 are negatively associated with the Bmi1 signaling pathway. Mechanistically, inhibition of the MPC complex-either genetically or pharmacologically-led to increased Bmi1 protein levels by reducing its ubiquitin-mediated degradation. These findings identify the MPC complex as a potential tumor suppressor and prognostic biomarker set in RCC, functioning in part through modulation of Bmi1 stability.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1253"},"PeriodicalIF":2.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}