Cellular Oncology最新文献

{"title":"Retraction Note: Leptin promotes the migration and invasion of breast cancer cells by upregulating ACAT2.","authors":"Yunxiu Huang, Qianni Jin, Min Su, Feihu Ji, Nian Wang, Changli Zhong, Yulin Jiang, Yifeng Liu, Zhiqian Zhang, Junhong Yang, Lan Wei, Tingmei Chen, Bing Li","doi":"10.1007/s13402-025-01035-y","DOIUrl":"10.1007/s13402-025-01035-y","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"265"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Downregulation of beta-catenin in chemo-tolerant TNBC through changes in receptor and antagonist profiles of the WNT pathway: Clinical and prognostic implications.","authors":"Saimul Islam, Hemantika Dasgupta, Mukta Basu, Anup Roy, Neyaz Alam, Susanta Roychoudhury, Chinmay Kumar Panda","doi":"10.1007/s13402-025-01036-x","DOIUrl":"10.1007/s13402-025-01036-x","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"267"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells.","authors":"Stanislav Drápela, Barbora Kvokačková, Eva Slabáková, Anna Kotrbová, Kristína Gömöryová, Radek Fedr, Daniela Kurfürstová, Martin Eliáš, Vladimír Študent, Frederika Lenčéšová, Ganji Sri Ranjani, Vendula Pospíchalová, Vítězslav Bryja, Wytske M van Weerden, Martin Puhr, Zoran Culig, Jan Bouchal, Karel Souček","doi":"10.1007/s13402-024-00982-2","DOIUrl":"10.1007/s13402-024-00982-2","url":null,"abstract":"<p><strong>Purpose: </strong>Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies.</p><p><strong>Methods: </strong>To address this, we employed a high-throughput single-cell flow cytometry approach to identify a specific surface fingerprint associated with docetaxel-resistance in PCa cells and complemented it with proteomic analysis of extracellular vesicles. We further validated selected antigens using docetaxel-resistant patient-derived xenografts in vivo and probed primary PCa specimens to interrogate of their surface fingerprint.</p><p><strong>Results: </strong>Our approaches revealed a 6-molecule surface fingerprint linked to docetaxel resistance in primary PCa specimens. We observed consistent overexpression of CD95 (FAS/APO-1), and SSEA-4 surface antigens in both in vitro and in vivo docetaxel-resistant models, which was also observed in a cell subpopulation of primary PCa tumors exhibiting EMT features. Furthermore, CD95, along with the essential enzymes involved in SSEA-4 synthesis, ST3GAL1, and ST3GAL2, displayed a significant increase in patients with PCa undergoing docetaxel-based therapy, correlating with poor survival outcomes.</p><p><strong>Conclusion: </strong>In summary, we demonstrate that the identified 6-molecule surface fingerprint associated with docetaxel resistance pre-exists in a subpopulation of primary PCa tumors before docetaxel treatment. Thus, this fingerprint warrants further validation as a promising predictive tool for docetaxel resistance in PCa patients prior to therapy initiation.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"205-218"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation BCMA-targeted chimeric antigen receptor CARTemis-1: the impact of manufacturing procedure on CAR T-cell features.","authors":"Belén Sierro-Martínez, Virginia Escamilla-Gómez, Laura Pérez-Ortega, Beatriz Guijarro-Albaladejo, Paola Hernández-Díaz, María de la Rosa-Garrido, Maribel Lara-Chica, Alfonso Rodríguez-Gil, Juan Luis Reguera-Ortega, Luzalba Sanoja-Flores, Blanca Arribas-Arribas, Miguel Ángel Montiel-Aguilera, Gloria Carmona, Maria Jose Robles, Teresa Caballero-Velázquez, Javier Briones, Hermann Einsele, Michael Hudecek, Jose Antonio Pérez-Simón, Estefanía García-Guerrero","doi":"10.1007/s13402-024-00984-0","DOIUrl":"10.1007/s13402-024-00984-0","url":null,"abstract":"<p><strong>Purpose: </strong>CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives is imperative. We present the preclinical and clinical validation of a new optimized anti-BCMA CAR (CARTemis-1). In addition, we explored how the manufacturing process could impact CAR-T cell product quality and fitness.</p><p><strong>Methods: </strong>CARTemis-1 optimizations were evaluated at the preclinical level both, in vitro and in vivo. CARTemis-1 generation was validated under GMP conditions, studying the dynamics of the immunophenotype from leukapheresis to final product. Here, we studied the impact of the manufacturing process on CAR-T cells to define optimal cell culture protocol and expansion time to increase product fitness.</p><p><strong>Results: </strong>Two different versions of CARTemis-1 with different spacers were compared. The longer version showed increased cytotoxicity. The incorporation of the safety-gene EGFRt into the CARTemis-1 structure can be used as a monitoring marker. CARTemis-1 showed no inhibition by soluble BCMA and presents potent antitumor effects both in vitro and in vivo. Expansion with IL-2 or IL-7/IL-15 was compared, revealing greater proliferation, less differentiation, and less exhaustion with IL-7/IL-15. Three consecutive batches of CARTemis-1 were produced under GMP guidelines meeting all the required specifications. CARTemis-1 cells manufactured under GMP conditions showed increased memory subpopulations, reduced exhaustion markers and selective antitumor efficacy against MM cell lines and primary myeloma cells. The optimal release time points for obtaining the best fit product were > 6 and < 10 days (days 8-10).</p><p><strong>Conclusions: </strong>CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00).</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"219-237"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional genome architecture in intrahepatic cholangiocarcinoma.","authors":"Youfeng Liang, Cong Li, Renchao Zou, Lu Ying, Xiaoyang Chen, Zhaohai Wang, Wenjing Zhang, Mingxuan Hao, Hao Yang, Rui Guo, Guanglin Lei, Fang Sun, Kexu Zhao, Yu Zhang, Jia Dai, Shangya Feng, Keyue Zhang, Luyuan Guo, Shuyue Liu, Chuanxing Wan, Lin Wang, Penghui Yang, Zhao Yang","doi":"10.1007/s13402-024-01033-6","DOIUrl":"https://doi.org/10.1007/s13402-024-01033-6","url":null,"abstract":"<p><strong>Purpose: </strong>Intrahepatic cholangiocarcinoma (ICC) is a common primary hepatic tumors with a 5-year survival rate of less than 20%. Therefore, it is crucial to elucidate the molecular mechanisms of ICC. Recently, the advance of high-throughput chromosome conformation capture (Hi-C) technology help us look insight into the three-dimensional (3D) genome structure variation during tumorigenesis. However, its function in ICC pathogenesis remained unclear.</p><p><strong>Methods: </strong>Hi-C and RNA-sequencing were applied to analyze 3D genome structures and gene expression in ICC and adjacent noncancerous hepatic tissue (ANHT). Furthermore, the dysregulated genes due to 3D genome changes were validated via quantitative real-time PCR and immunohistochemistry.</p><p><strong>Results: </strong>Primarily, the intrachromosomal interactions of chr1, chr2, chr3, and chr11 and the interchromosomal interactions of chr1-chr10, chr13-chr21, chr16-chr19, and chr19-chr22 were also significantly distinct between ANHT and ICC, which may potentially contribute to the activation of cell migration and invasion via the upregulation of WNT10A, EpCAM, S100A3/A6, and MAPK12. Interestingly, 56 compartment regions from 23 chromosomes underwent A to B or B to A transitions during ICC oncogenesis, which attenuated the complement pathway through the downregulation of C8A/C8B, F7, F10, and F13B. Notably, topologically associated domain (TAD) rearrangements were identified in the region containing HOPX (chr4: 57,514,154-57,522,688) and ACVR1 (chr2:158,592,958-158,732,374) in ICC, which may contribute to the hijacking of remote enhancers that were previously outside the TAD and increased expression of HOPX and ACVR1.</p><p><strong>Conclusions: </strong>This study reveals relationship between 3D genome structural variations and gene dysregulation during ICC tumorigenesis, indicating the molecular mechanisms and potential biomarkers.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE2Q2 promotes tumor progression and glycolysis of hepatocellular carcinoma through NF-κB/HIF1α signal pathway.","authors":"Xiaoling Wu, Yiran Chen, Wenzhi He, Ye Yao, Yingyi Liu, Peng Xia, Hao Zhang, Xiaomian Li, Yonghua Guo, Xi Chen, Weijie Ma, Yufeng Yuan","doi":"10.1007/s13402-025-01037-w","DOIUrl":"https://doi.org/10.1007/s13402-025-01037-w","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic reprogramming, particularly the Warburg effect, plays a crucial role in the onset and progression of tumors. The ubiquitin-conjugating enzyme E2 Q2 (UBE2Q2) has been identified overexpressed in hepatocellular carcinoma (HCC). Our aim was to determine if UBE2Q2 plays a role in regulating glycolysis, contributing to the carcinogenesis of HCC.</p><p><strong>Methods: </strong>Bioinformatics analysis, western blot and qPCR were used to detect the expression of UBE2Q2. Functional experiments, proteomics analysis and subcutaneous tumors were constructed to find the biological function of UBE2Q2 in HCC. Co-immunoprecipitation, western blot and ubiquitination assays were used to identify the mechanisms involved.</p><p><strong>Results: </strong>We found a significant association between high UBE2Q2 expression and poor prognosis in HCC patients. Functionally, UBE2Q2 was shown to advance tumor progression in HCC through both in vitro assays and in vivo assessments. Proteomics analysis and glycolysis stress tests corroborated an increase in glycolytic activity due to UBE2Q2. Our findings reveal that UBE2Q2 augments glycolysis by boosting the transcription levels of hypoxia-inducible factor 1α (HIF1α), primarily through the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. At the molecular level, UBE2Q2 interaction with baculoviral IAP repeat-containing 2 (cIAP1) orchestrates the K63-linked ubiquitination of receptor-interacting serine/threonine-protein kinase 1 (RIP1), which in turn, activates the NF-κB signaling pathway.</p><p><strong>Conclusions: </strong>Our investigation reveals that UBE2Q2 regulates the glycolysis in HCC through modulation of the NF-κB/HIF1α signaling pathway, pinpointing UBE2Q2 as a promising therapeutic target for the disease.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of a regulatory T cells-based classification of renal cell carcinoma: an integrated bioinformatic analysis and clinical cohort study.","authors":"Yuntao Yao, Yifan Liu, Bingnan Lu, Guo Ji, Lei Wang, Keqin Dong, Zihui Zhao, Donghao Lyu, Maodong Wei, Siqi Tu, Xukun Lyu, Yuanan Li, Runzhi Huang, Wang Zhou, Guofeng Xu, Xiuwu Pan, Xingang Cui","doi":"10.1007/s13402-024-01030-9","DOIUrl":"https://doi.org/10.1007/s13402-024-01030-9","url":null,"abstract":"<p><strong>Purpose: </strong>Renal cell carcinoma (RCC), exhibiting remarkable heterogeneity, can be highly infiltrated by regulatory T cells (Tregs). However, the relationship between Treg and the heterogeneity of RCC remains to be explored.</p><p><strong>Methods: </strong>We acquired single-cell RNA-seq profiles and 537 bulk RNA-seq profiles of TCGA-KIRC cohort. Through clustering, monocle2 pseudotime and prognostic analyses, we identified Treg states-related prognostic genes (TSRPGs), then constructing the RCC Treg states-related prognostic classification (RCC-TSC). We also explored its prognostic significance and multi-omics landmarks. Additionally, we utilized correlation analysis to establish regulatory networks, and predicted candidate inhibitors. More importantly, in Xinhua cohort of 370 patients with kidney neoplasm, we used immunohistochemical (IHC) staining for classification, then employing statistical analyses including Chi-square tests and multivariate Cox proportional hazards regression analysis to explore its clinical relevance.</p><p><strong>Results: </strong>We defined 44 TSRPGs in four different monocle states, and identified high immune infiltration RCC (HIRC, LAG3+, Mki67+) as the highly exhausted subtype with the worst prognosis in RCC-TSC (p < 0.001). BATF-LAG3-immune cells axis might be its underlying metastasis-related mechanism. Immunotherapy and inhibitors including sunitinib potentially conferred best therapeutic effects for HIRC. Furthermore, we successfully validated HIRC subtype as an independent prognostic factor within the Xinhua cohort (OS, HR = 16.68, 95% CI = 1.88-148.1, p = 0.011; PFS, HR = 4.43, 95% CI = 1.55-12.6, p = 0.005).</p><p><strong>Conclusion: </strong>Through integrated bioinformatics analysis and a large-sample retrospective clinical study, we successfully established RCC-TSC and a diagnostic kit, which could stratify RCC patients with different prognosis and to guide personalized treatment.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The origin of patient-derived cancer organoids from pathologically undiagnosed specimen in patients with pancreatobiliary cancers.","authors":"Bomi Kim, Jiho Park, Hee Young Na, Sinwoo Park, Jeonghwa Jin, Kwangrok Jung, Jong-Chan Lee, Jin-Hyeok Hwang, Minseok Seo, Jaihwan Kim","doi":"10.1007/s13402-024-01026-5","DOIUrl":"https://doi.org/10.1007/s13402-024-01026-5","url":null,"abstract":"<p><strong>Purpose: </strong>Tissue confirmation of pancreatobiliary cancer is often difficult because of the location of the tumor and structure of the surrounding blood vessels. Patient-derived cancer organoids (PDCOs) reflect the genomic characteristics of individual cancers. Although diverse attempts to construct PDCOs for various pancreatobiliary cancer models are ongoing, no research results have yet confirmed the possibility of performing a precise diagnosis on PDCOs derived from pathologically negative patient samples.</p><p><strong>Methods: </strong>We obtained a total of nine samples, including pathologically negative samples, from four patients (three patients with pancreatic cancer and one patient with gallbladder cancer) using different tissue acquisition methods to establish PDCOs (success rate 75%).</p><p><strong>Results: </strong>We successfully verified whether the constructed PDCOs could represent the tissues of patients with pancreatobiliary cancer at each multi-omics level using tumor panel sequencing, single-cell RNA sequencing, hematoxylin and eosin, and immunohistochemical staining. PDCOs from pathologically negative samples showed expression patterns of malignant ductal cell-related biomarkers similar to those of other pathologically positive samples. Furthermore, the expression patterns at the single-cell level in PDCO from patients ultimately diagnosed with gallbladder cancer after surgery were different from those in patients with pancreatic cancer.</p><p><strong>Conclusion: </strong>Therefore, our study implicated the potential of PDCOs as diagnostic and research tools, including for case involving limited tissue samples. Based on these results, we anticipate that this could be extended to more advanced studies, such as drug sensitivity testing, through large-scale trials in the near future.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.","authors":"Ge Sun, Chunguang Zhao, Jing Han, Shaoya Wu, Yan Chen, Jing Yao, Li Li","doi":"10.1007/s13402-024-01011-y","DOIUrl":"10.1007/s13402-024-01011-y","url":null,"abstract":"<p><p>Regulation of steroid hormone receptors (SHRs) on transcriptional reprogramming is crucial for breast cancer progression. SHRs, including estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) play key roles in remodeling the transcriptome of breast cancer cells. However, the molecular mechanisms by which SHRs regulate chromatin landscape in enhancer regions and transcription factor interactions remain largely unknown. In this review, we summarized the regulatory effects of 3 types of SHRs (AR, PR, and GR) on gene transcription through chromatin interactions and enhancer reprogramming. Specifically, AR and PR exhibit bi-directional regulatory effects (both inhibitory and promoting) on ER-mediated gene transcription, while GR modulates the transcription of pro-proliferation genes in ER-positive breast cancer cells. In addition, we have presented four enhancer reprogramming mechanisms (transcription factor cooperation, pioneer factor binding, dynamic assisted loading, and tethering) and the multiple enhancer-promoter contact models. Based on these mechanisms and models, this review proposes that the combination of multiple therapy strategies such as agonists/antagonists of SHRs plus endocrine therapy and the adoption of the latest sequencing technologies are expected to improve the efficacy of ER positive breast cancer treatment.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"2073-2090"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP28 promotes tumor progression and glycolysis by stabilizing PKM2/Hif1-α in cholangiocarcinoma.","authors":"Qian Qiao, Jifei Wang, Shuochen Liu, Jiang Chang, Tao Zhou, Changxian Li, Yaodong Zhang, Wangjie Jiang, Yananlan Chen, Xiao Xu, Mingyu Wu, Xiangcheng Li","doi":"10.1007/s13402-024-01002-z","DOIUrl":"10.1007/s13402-024-01002-z","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitination is one of the important modification of proteins which can be reversed by deubiquitinating enzymes (DUBs). Ubiquitin specific protease 28 (USP28) belongs to the deubiquitinase family, which plays a cancer-promoting function in many types of cancers such as pancreatic cancer and breast cancer. So far, the molecular function and significance of USP 28 in cholangiocarcinoma remain unclear.</p><p><strong>Methods: </strong>In this study, we evaluated the expression of USP28 using tissue microarray (TMA), reverse transcription polymerase chain reaction (qRT-PCR), and online databases. We investigated the effect of USP28 on the progression of CCA through in vitro and in vivo functional experiments. In addition, we explored downstream molecular pathways using Western blotting (WB), immunofluorescence (IF), and mass spectrometry techniques.</p><p><strong>Results: </strong>Here, we found that cholangiocarcinoma tissue had higher USP 28 expression than normal bile duct tissue, and that high USP 28 levels were significantly associated with a malignant phenotype and poorer prognosis in cholangiocarcinoma patients. Both in vitro and in vivo, USP28 could mediate the deubiquitination of PKM2, thereby activating the downstream Hif1-α signaling pathway, promoting glycolysis and energy supply, and finally promoting tumor progression.</p><p><strong>Conclusion: </strong>In summary, USP28 activated downstream Hif1-α by reducing the ubiquitination level of PKM2, furthermore, promoting the level of glycolysis in CCA cells for tumor progression.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"2217-2231"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}