IUBMB Life最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148069702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148069701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics Analysis Reveals That the MAZ/HDGF Regulatory Axis Drives High-Grade Serous Ovarian Cancer Progression by Modulating Glycolysis and M2 Macrophage Polarization","authors":"Ji Liu,&nbsp;Yong-hong Luo,&nbsp;Su Wan,&nbsp;Guan-tai Ni","doi":"10.1002/iub.70080","DOIUrl":"10.1002/iub.70080","url":null,"abstract":"<div>\u0000 \u0000 <p>Super-enhancers (SEs) are large clusters of enhancers that drive high-level expression of genes critical for normal development and tumorigenesis. However, their precise roles in high-grade serous ovarian carcinoma (HGSOC) remain unclear. This study integrated SE-derived regulatory networks with proteomic profiles to identify key pro-tumorigenic signaling in HGSOC progression. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to screen SE-driven core oncoproteins. The influence on cell phenotypes was evaluated by detecting invasion, proliferation, apoptosis, glucose consumption, lactate generation, and tube formation. M2 macrophage polarization was assessed by detecting CD163⁺ cell proportion and TGF-β1 and IL-10 secretion. The MAZ/HDGF interaction was confirmed by luciferase and ChIP-qPCR assays. Xenograft studies were used to evaluate the in vivo function. HDGF was overexpressed and was identified as a core SE-driven oncoprotein in HGSOC. Silencing of HDGF inhibited the invasion, proliferation, and glycolysis of HGSOC cells, promoted their apoptosis, and attenuated HUVEC tube formation and M2 macrophage polarization. Mechanistically, MAZ transcriptionally activated HDGF through promoter binding. Moreover, HDGF re-expression counteracted the suppressive effects of MAZ knockdown on HGSOC cell malignant behaviors, HUVEC tube formation, M2 macrophage polarization, and the growth of xenograft tumors. In conclusion, our study unveils the MAZ/HDGF axis as a novel SE-mediated oncogenic pathway in HGSOC, providing previously unrecognized insights into SE-driven oncogenesis and highlighting potential targets for HGSOC treatment.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capturing the Variations in Mutant p53-Driven Regulatory Networks in Breast Cancer Subtypes, Its Clinical Relevance and a Novel Association With Androgen Receptor and EMT","authors":"Aastha Singh,&nbsp;Rahul Gupta,&nbsp;Ritu Kulshreshtha","doi":"10.1002/iub.70081","DOIUrl":"10.1002/iub.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>The tumour suppressor <i>TP53</i> is frequently mutated in breast cancer and drives poor outcomes. The impact of mutant p53 (mutp53) on subtype-specific gene and non-coding RNA networks, and their clinical significance, remains largely underexplored. Here, using TCGA-BRCA data, we have delineated subtype-specific mRNA, lncRNA, and microRNA signatures, pathways, co-expression/interaction networks, and prognosis associated with hotspot mutp53 or wildtype p53 tumours. Our study shows that mutp53 deregulates the genes related to EMT, chemoresistance, and prognosis in a subtype-specific manner. The EMT-associated signature was able to stratify HER2 and Basal patients by their p53 status. Construction of lncRNA-mRNA-miRNA interaction networks led to the identification of various feedback loops and hub genes with prognostic relevance that possess binding sites for p53 and EMT-TFs within their promoters. In the basal mutp53 tumours, we found Androgen Receptor (<i>AR)</i> to be a downregulated EMT-associated gene, with its higher levels linked to a better prognosis. We validated that mutp53 breast cancer cell lines show reduced levels of <i>AR</i> and its predicted transcriptional target, miR-196a-5p. Overexpression of WTp53 resulted in the upregulation of AR and miR-196a-5p, while mutp53 (R175H) suppressed their expression. Basal mutp53 tumours with low AR displayed higher EMT scores. Enforced expression of AR led to suppression of mesenchymal markers in basal cell lines. Overall, we have identified novel prognostically relevant RNA signatures and networks that may serve as attractive therapeutic targets in mutp53 breast cancer patients in a subtype-specific manner. Additionally, we have discovered a novel AR:mutp53 association that may be implicated in EMT and chemoresistance.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Methylglyoxal on Intestinal Cells: Insights on Epigenetic Regulatory Enzymes","authors":"Camilla Morresi,&nbsp;Giulia Feliziani,&nbsp;Luisa Bellachioma,&nbsp;Christian Giommi,&nbsp;Rosita Gabbianelli,&nbsp;Laura Bordoni,&nbsp;Gianna Ferretti,&nbsp;Tiziana Bacchetti,&nbsp;Elisabetta Damiani","doi":"10.1002/iub.70067","DOIUrl":"10.1002/iub.70067","url":null,"abstract":"<p>Methylglyoxal (MGO) is endogenously produced under physiological conditions as a by-product of glycolysis and by autooxidation of glucose and lipid peroxidation. The digestive system can also take up MGO from exogenous sources, especially from ultra-processed foods. MGO is a highly reactive molecule, able to react with macromolecules forming covalent adducts resulting in advanced glycation end-products formation. MGO can also enter the nucleus and react with nucleic acids with the formation of MGO-nucleic acid adducts. The intestinal epithelium is continuously exposed to dietary and endogenous stimuli, including MGO, but the potential harmful role of MGO at the intestinal level has been poorly investigated. Therefore, the aim of the study was to further investigate the effects of MGO in intestinal cells and the molecular mechanisms involved, with particular attention to epigenetic regulatory enzymes such as histone deacetylases (HDAC), ten-eleven translocation (TET) family enzymes, and DNA methyltransferases (DNMT). Our results demonstrate that MGO exposure induces alterations in intestinal barrier function in differentiated Caco-2 cells monolayers. Moreover, MGO treatment induces cell apoptosis associated with an increase in cytosolic and mitochondrial reactive oxygen species. MGO-induced oxidative stress was associated with activation of the NFκB pathway and increased levels of proinflammatory molecules such as TNF-α and antioxidant enzymes (superoxide dismutase 1 [SOD1] and catalase). The increased expression of γH2AX suggests damage to DNA in MGO-treated cells. A decrease in HDAC1/2 expression, consistent with the increase in acetylated histone H4 levels, and an inhibition of the expression of TET (TET1, TET2) proteins was observed in MGO-treated cells. These results suggest that MGO may also disrupt epigenetic homeostasis mechanisms, offering further insight into the pathways through which MGO causes cellular damage in intestinal cells.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Macrophage-Derived 7-Gene Signature Predicts Prognosis and Therapeutic Response in Hepatocellular Carcinoma","authors":"Xiaomin Li,&nbsp;Zhilong Li,&nbsp;Jinfang Zhai,&nbsp;Binbin Zou","doi":"10.1002/iub.70079","DOIUrl":"10.1002/iub.70079","url":null,"abstract":"<p>This study aimed to identify a novel prognostic signature derived from an EGFR Tyrosine kinase inhibitors (TKI-resistant) macrophage subpopulation and to evaluate its clinical and therapeutic relevance in HCC. We utilized single-cell RNA sequencing data from HCC patients. An EGFR-TKI resistance score was calculated across all cell types. Macrophages, which exhibited the highest resistance score, were sub-clustered to identify the most resistant subpopulation. Marker genes from this sub-cluster were intersected with differentially expressed genes (DEGs) from the TCGA-LIHC cohort. A robust prognostic model was constructed. The model's performance was rigorously validated, and the signature was further characterized through multi-omics analysis and its correlation with immune checkpoint blockade (ICB) response and drug sensitivity. scRNA-seq analysis unequivocally identified macrophages as possessing the highest EGFR-TKI resistance score. We identified seven key prognostic genes: <i>SLC41A3</i>, <i>DCAF13</i>, <i>PPM1G</i>, <i>NDC80</i>, <i>FAM83D</i>, <i>FUCA2</i>, and <i>UQCRH</i>. A risk model built on these seven genes effectively stratified patients into high- and low-risk groups with significantly different overall survival (OS) in the TCGA cohort, a finding successfully validated in the independent GSE76427 cohort. A clinical nomogram integrating the risk score demonstrated excellent predictive accuracy, with AUC values for 1-, 3-, and 5-year OS of 0.816, 0.781, and 0.799, respectively. The low-risk group was associated with a favorable immune-infiltrated phenotype and was predicted to be more sensitive to immunotherapy. Conversely, the high-risk group exhibited distinct genomic features and was predicted to be more sensitive to specific targeted agents, including Navitoclax and Sorafenib. We identified and validated a novel 7-gene prognostic signature derived from a subpopulation of EGFR-TKI-resistant macrophages. This signature accurately predicts patient survival, offers insights into the molecular mechanisms of therapy resistance in HCC, and provides a promising tool for improved patient stratification and the development of personalized treatment strategies.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic Role of PTPN14 in Pancreatic Cancer Through β-Catenin/NF-κB Pathway Activation","authors":"Danni Luo,&nbsp;Xiaopan Luo,&nbsp;Shaojie Qian,&nbsp;Jintao Liu","doi":"10.1002/iub.70078","DOIUrl":"10.1002/iub.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Pancreatic cancer (PC) is one of the deadliest malignancies due to early metastasis, therapy resistance, and a highly immunosuppressive microenvironment. Although oncogenic mutations such as <i>KRAS</i> and <i>TP53</i> are well characterized, the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14)—a Hippo-pathway regulator implicated in other cancers—remains unclear in PC. PTPN14 expression was analyzed in PC tissues and cell lines using immunohistochemistry and western blotting. Functional effects of PTPN14 knockdown or overexpression on proliferation, apoptosis, migration, and invasion were evaluated in vitro using CCK-8, flow cytometry, wound healing, and Transwell assays. Molecular mechanisms were explored via western blotting, immunofluorescence, and rescue experiments focusing on β-catenin and NF-κB signaling. In vivo, a xenograft mouse model assessed tumor growth, histopathology, apoptosis (TUNEL), Ki67 expression, and serum cytokine levels (ELISA). PTPN14 was markedly upregulated in PC tissues and cell lines. Silencing PTPN14 significantly inhibited cell proliferation, migration, and invasion, while enhancing apoptosis in vitro. Mechanistically, PTPN14 activated β-catenin and NF-κB signaling, promoting β-catenin nuclear translocation and p65 phosphorylation, with increased IL-6, TNF-α, and IL-1β secretion. In vivo, PTPN14 knockdown suppressed xenograft tumor growth, reduced Ki67 expression, enhanced apoptosis, and lowered serum pro-inflammatory cytokines. PTPN14 drives PC progression by co-activating β-catenin and NF-κB pathways and promoting a pro-tumor inflammatory milieu. These findings highlight PTPN14 as a promising therapeutic target to inhibit PC aggressiveness and inflammation-driven tumor progression.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}