Biological Procedures Online最新文献

{"title":"A novel prognostic model based on MVIRGs identifies ANGPT2 as a key target driving the malignant progression of HCC.","authors":"Xian Li, Zhouli Tan, Shanru Feng, Qiang Yu, Jian Zhou, Jia Fan, Yang Xu","doi":"10.1186/s12575-026-00347-z","DOIUrl":"10.1186/s12575-026-00347-z","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly lethal malignancy with high recurrence and limited therapies. Microvascular invasion (MVI) is a critical prognostic factor, but its molecular mechanisms and precise predictive tools are lacking. This study aimed to identify key MVI-associated genes (MVIRGs), develop a prognostic model, and elucidate the role of ANGPT2 in HCC progression and therapeutic responses.</p><p><strong>Methods: </strong>Machine learning on multi-cohort data (TCGA, ICGC) identified MVIRGs and constructed a prognostic model. ANGPT2, the core oncogenic MVIRG, was validated clinically (IHC) and functionally (in vitro and in vivo). We analyzed its association with the tumor immune microenvironment (TIME), immune checkpoint inhibitors (ICIs), and drug sensitivity.</p><p><strong>Results: </strong>A powerful six-MVIRG prognostic model was developed, with ANGPT2 identified as the sole oncogenic gene. Clinically, ANGPT2 was significantly overexpressed, correlating strongly with aggressive features like MVI, vascular invasion, and advanced stages, serving as a robust poor prognostic biomarker for OS and PFS. Functionally, ANGPT2 knockdown significantly inhibited HCC cell growth and migration in vitro, and inhibited tumor growth in vivo. Bioinformatics revealed ANGPT2 fosters an immunosuppressive TIME, upregulating immune checkpoints (e.g., PD-L1) to mediate resistance to ICIs. High ANGPT2 expression showed a differential drug response: resistance to targeted therapies (e.g., EGFR-TKIs) but paradoxically increased sensitivity to chemotherapies (e.g., docetaxel, paclitaxel).</p><p><strong>Conclusion: </strong>This study constructed a powerful MVIRG model and identified ANGPT2 as a core oncogenic molecule. ANGPT2 drives HCC progression, mediates immune resistance, and differentially regulates drug sensitivity, making it a key biomarker for prognosis and treatment guidance.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052243","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":"Lipid Metabolic Rewiring During Continuous Prostate Cancer Progression Defines a Biologically Relevant Four-Gene Prognostic Signature.","authors":"Rongna Li, Hongying He, Hui Sun, Yili Long, Nan Huang, Yingbing Zhu, Hongtao Chen, Guanmin Jiang, Xiaohui Chen","doi":"10.1186/s12575-026-00345-1","DOIUrl":"10.1186/s12575-026-00345-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lipid metabolic reprogramming is increasingly recognized as a critical feature of prostate cancer progression, but the lipid metabolism-related genes that remain continuously dysregulated from normal tissue to primary tumor and metastatic disease have not been systematically characterized, and their biological and prognostic relevance remains incompletely understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To identify lipid metabolism-related genes associated with continuous prostate cancer progression and develop a prognostic signature for survival stratification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical prostate cancer specimens and a high-fat diet (HFD)-driven RM-1 tumor model were first used to evaluate lipid metabolic alterations in vivo. GSE6919 transcriptomic data were used to identify genes shared between the Normal-Primary and Primary-Metastatic transitions. These genes were intersected with a curated lipid metabolism-related gene set, followed by GO and KEGG enrichment analyses. TCGA prostate adenocarcinoma expression and clinical data were used for LASSO regression to construct a prognostic model. The four core genes were further evaluated by clinicopathological correlation analysis, protein- and transcript-level validation in clinical tissues and prostate cancer cell lines, and functional assays under oleic acid-induced lipid stress. Immune infiltration analysis, ssGSEA, and nomogram analysis were performed to assess the biological and clinical relevance of the model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Clinical tissues showed increased PLIN3 expression, and HFD feeding promoted tumor growth and reinforced lipid metabolic alterations in vivo. A total of 44 lipid metabolism-related genes were identified as continuously dysregulated during prostate cancer progression. These genes were mainly enriched in fatty acid metabolism, lipid catabolism, peroxisome, lipid droplet, glycolysis/gluconeogenesis, arachidonic acid metabolism, and PPAR signaling. Eight genes were significantly associated with overall survival in TCGA, and a four-gene signature comprising ALDH3A2, ENO2, PPP1CB, and PTGIS was established. This model effectively stratified patients into high- and low-risk groups with significantly different survival outcomes. The risk score was positively associated with clinical T stage and Gleason score. The four core genes were also associated with lipid metabolic enzymes, immune infiltration patterns, and multiple metabolism-related pathways. Protein- and transcript-level validation in clinical tissues and prostate cancer cell lines supported the biological relevance of the signature, although PTGIS showed a more context-dependent pattern. Functionally, silencing ENO2 reduced oleic acid-induced lipid peroxidation, whereas silencing PPP1CB enhanced it, while ALDH3A2 showed a more context-dependent effect. A nomogram integrating the risk score with clinical variables improved individualized survival prediction.&lt;/p&gt;&lt;p","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013364","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":"Targeting Hyaluronan Signaling Overcomes Primary Effusion Lymphoma Cells Resistance to Rapamycin.","authors":"Jungang Chen, Margaret Qin, Jiaojiao Fan, Shengyu Mu, Lu Dai, Zhiqiang Qin","doi":"10.1186/s12575-026-00346-0","DOIUrl":"10.1186/s12575-026-00346-0","url":null,"abstract":"<p><p>The oncogenic γ-herpesvirus known as the Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of several cancers arising in patients with compromised immune systems. One of KSHV-related malignancies, primary effusion lymphoma (PEL), comprises transformed B cells harboring the viral episome and arises preferentially within the pleural or peritoneal cavities of patients including those with HIV infection. PEL is a rapidly progressing malignancy with a median survival time of several months even with conventional chemotherapy. One of the major reasons causing PEL chemotherapy failure is multidrug chemoresistance of lymphoma cells, however, there are only limited data exploring the mechanisms of PEL chemoresistance. In the current study, we demonstrate the role of hyaluronan (HA) signaling activation in rapamycin resistance in PEL cells, and that targeting HA signaling by small HA oligosaccharides (oHA) can augment rapamycin efficacy against PEL expansion in vivo. Our results provide the framework for the development of HA-targeted therapies clinical trials for PEL patients, which may represent promising adjuncts to reduce chemotherapy toxicity, improve treatment and prolong patients' survival.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004378","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":"Activation of PPARγ and CPT1A Mediates the Hepatoprotective Effect of Ginsenoside CK against NAFLD in Rats.","authors":"Danfeng Lan, Guishun Sun, Zhiyong Dong, Kunlin Li, Shiwen Li, Xuan He, Rongzhuang Zou, Wei Yang, Junyu Wang, Bian Wu","doi":"10.1186/s12575-026-00340-6","DOIUrl":"10.1186/s12575-026-00340-6","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) is a significant underlying driver of hepatocellular carcinoma; however, current clinical treatment options remain limited. Ginsenoside CK (CK), a natural bioactive compound, has shown promise in modulating lipid metabolism and protecting liver function. Nevertheless, its therapeutic potential against the pathogenesis of NAFLD and the associated molecular pathways is not fully understood. This study employed an integrated strategy that combines transcriptomic analysis with both in vivo and in vitro validation, utilizing a high-fat diet (HFD)-induced rat model to elucidate the efficacy and molecular mechanisms of CK in ameliorating NAFLD.</p><p><strong>Methods: </strong>An NAFLD rat model was established through HFD feeding to assess the effects of CK on various physiological and biochemical parameters, thereby clarifying its role in regulating lipid metabolism and providing hepatoprotection in vivo. Additionally, a free fatty acid (FFA)-induced Huh7 cell model was constructed to evaluate the in vitro activity of CK in promoting lipid metabolism and inhibiting lipid accumulation. Subsequently, transcriptomic analysis was conducted to identify potential targets and elucidate the mechanisms underlying the effects of CK. Finally, the proposed mechanism was verified through in vivo experiments.</p><p><strong>Results: </strong>In vivo results indicated that CK treatment significantly mitigated the increases in body weight and organ indices induced by a HFD. Additionally, CK improved biochemical parameters in both liver and serum, alleviated liver injury, steatosis, and insulin resistance, thereby providing a protective effect on liver tissue. Furthermore, CK markedly reduced the deposition of intracellular lipid droplets in hepatocytes. It also enhanced the expression of fatty acid metabolism-related genes, CPT1 and CPT2, in the liver, while downregulating the expression of lipogenic genes, including ACC1, FAS, and SREBP1c. Mechanistic investigations revealed that CK modulates the PPARγ/CPT1A signaling axis, suppresses the expression of hepatic lipogenic genes, reduces lipid accumulation, and consequently improves insulin resistance and liver injury.</p><p><strong>Conclusion: </strong>Our study demonstrates that CK attenuates NAFLD progression by regulating the PPARγ/CPT1A signaling axis.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970242","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":"Ethnopharmacological evaluation and metabolic mechanism of Sanjie Xiaoliu Granule in breast cancer with depression.","authors":"Zhuo Liu, Tianhao Tong, Renyi Yang, Puhua Zeng","doi":"10.1186/s12575-026-00334-4","DOIUrl":"10.1186/s12575-026-00334-4","url":null,"abstract":"<p><strong>Background: </strong>Sanjie Xiaoliu Granule (SJXLG), a traditional multi-herbal prescription widely used in Chinese medicine, has been historically applied to \"disperse nodules, soothe the liver, and relieve depression.\" It is clinically prescribed for patients with breast lumps, emotional stagnation, and cancer-related depression. However, the pharmacological basis underlying its dual anticancer and antidepressant effects remains poorly understood.This study aimed to evaluate the therapeutic efficacy and elucidate the molecular and metabolic mechanisms of SJXLG in breast cancer with depression (BCD) through integrated experimental and bioinformatics approaches. In vivo and in vitro BCD models were established to assess tumor growth, behavioral performance, and inflammatory cytokine levels. Liquid chromatography-mass spectrometry (LC-MS) identified active constituents of SJXLG. Bioinformatics analyses were used to screen key genes and signaling pathways, followed by validation via qRT-PCR and Western blot. Untargeted metabolomics was applied to explore the metabolic alterations in tumor tissues after SJXLG intervention.</p><p><strong>Results: </strong>SJXLG significantly inhibited breast cancer cell proliferation, migration, and invasion, and improved depressive-like behaviors in tumor-bearing mice. The formula upregulated MAOA, LTF, PTGER3, and IGFBP6 expression and regulated multiple signaling pathways, including PPAR, AMPK, and PI3K-Akt/mTOR, which are involved in lipid metabolism, inflammation, and neurotransmitter synthesis. Untargeted metabolomics further revealed that SJXLG restored metabolic homeostasis by modulating lipid, amino acid, and energy metabolism, alleviating oxidative stress, and rebalancing neurotransmitter-related metabolites. These findings suggest that SJXLG exerts integrative effects through multi-target, multi-pathway regulation.</p><p><strong>Conclusions: </strong>SJXLG demonstrates a synergistic anticancer and antidepressant effect through the modulation of metabolic and signaling networks associated with inflammation, oxidative stress, and neurotransmission. These results provide experimental evidence for its ethnopharmacological application in managing body-mind comorbidities such as breast cancer with depression and highlight its potential as a safe and effective adjunct therapy.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970288","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":"Identification and validation of serum SLIT1 as a biomarker for predicting anti-PD-1/PD-L1 resistance in non-small cell lung cancer.","authors":"Huisi Qiu, Cong Peng, Ziao Gao, Huafeng Luo, Ying Wei, Yuanfeng Huang, Danyang Chen, Ying Song, Kai Luo, Hao Liu, Xin Lin, Qian Wang","doi":"10.1186/s12575-026-00344-2","DOIUrl":"10.1186/s12575-026-00344-2","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC), the predominant subtype of lung cancer, contributes greatly to cancer-related mortality worldwide. Although inhibitors of programmed cell death protein 1 (PD-1) and its ligand PD-L1 have markedly improved patient outcomes, treatment resistance remains a substantial clinical challenge, underscoring the need for more effective predictive biomarkers. This study aimed to identify novel biomarkers for predicting treatment efficacy and clinical prognosis by systematically analyzing serum protein profiles of patients with divergent immunotherapy responses using four-dimensional data-independent acquisition (4D-DIA) proteomics integrated with the DB4000 platform.</p><p><strong>Results: </strong>A total of 49 differentially expressed proteins were identified between treatment-resistant and treatment-sensitive patients, with Slit Guidance Ligand 1 (SLIT1) exhibiting the most pronounced downregulation (log₂[fold-change] ≈ - 2.29, P = 0.0419). In an independent validation cohort, enzyme-linked immunosorbent assay indicated that SLIT1 expression was significantly higher in resistant patients than in sensitive patients (P < 0.0001). Furthermore, elevated SLIT1 expression was independently associated with shorter progression-free survival. A prognostic model integrating SLIT1 with other clinical variables demonstrated excellent discriminative performance (area under the curve = 0.964, 95% confidence interval: 0.929-0.998). Single-cell transcriptomic analysis further revealed a significant enrichment of SLIT1 expression within myeloid-lineage cells, particularly in M2-polarized macrophages (P = 0.0396), suggesting its involvement in modulating an immunosuppressive tumor microenvironment that may underlie treatment resistance.</p><p><strong>Conclusions: </strong>By employing an integrated multiomics framework, this study validated serum SLIT1 as a pivotal biomarker for predicting resistance to PD-1/PD-L1 inhibitors in patients with NSCLC and concurrently elucidated its correlation with an immunosuppressive tumor microenvironment. These findings not only offer a potential predictive tool for clinical application but also lay the groundwork for future mechanistic investigations and the development of optimized therapeutic strategies.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940024","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":"Prognostic Significance and Immune Landscape of Neuroendocrine Differentiation-Related Genes in Non-Small Cell Lung Cancer.","authors":"Tong Li, Meidan Luo, Sibo Peng, Jianguo Zhong, Fan Ren, Jingliang Gan, Huangsheng Xie, Jiayue Qiao, Chicheng Liu, Jia Li, Song Xu","doi":"10.1186/s12575-026-00343-3","DOIUrl":"10.1186/s12575-026-00343-3","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy resistance represents a current research hotspot. Previous studies found that neuroendocrine differentiation (NED) might significantly contribute to the initiation and development of non-small cell lung cancer (NSCLC). However, the interplay between immunotherapy resistance and NED in NSCLC remains unclear. This study explored the relationships between NED-related genes (NEDRGs) and immunotherapy resistance-related genes in NSCLC.</p><p><strong>Methods: </strong>Control and NSCLC samples, including NSCLC samples exposed to PD-1 blockade, were selected from public databases to identify differentially expressed genes (DEGs). Then, univariate Cox regression analysis and the proportional hazards assumption test were performed to identify prognostic genes based on the DEGs and NEDRGs, and a risk model was developed and validated. Thereafter, a nomogram was established. Subsequently, gene set enrichment analysis (GSEA), immune analysis, and drug sensitivity analysis were conducted. The key cells were ascertained in a single-cell RNA sequencing dataset. We collected specimens from six patients at Tianjin Medical University General Hospital and validated them using quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Three prognostic genes (RRM2, WDR76, and PLEKHH2) were identified, and the developed risk model could predict the survival of patients with NSCLC. The nomogram had good predictive ability concerning survival rates in NSCLC. Based on the GSEA results, a notable pathway in the two risk groups included cell cycle pathways, and prognostic genes were all enriched in these pathways. Furthermore, activated memory CD4⁺ T cells might contribute significantly to survival, and 109 drugs, including AZD6738, could be candidate treatments for NSCLC. Epithelial cells were identified as the key population in which the expression of prognostic genes was altered significantly across different developmental stages. RT-qPCR and IHC confirmed that RRM2 and WDR76 expression was higher in cancer tissues than in normal tissues, increasing with disease progression, whereas PLEKHH2 exhibited the opposite trend.</p><p><strong>Conclusion: </strong>The developed risk model based on three prognostic genes (RRM2, WDR76, and PLEKHH2) exhibited superior predictive accuracy in NSCLC. These results may provide new insights for investigating novel therapeutic targets in NSCLC.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925851","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":"4-Hydroxychalcone Exert the Anti-cancer Potential in Colorectal Cancer Through Targeting CDK6.","authors":"Chenxin Yang, Mingxuan Huangfu, Xintong Dai, Lumeng Liu, Huifang Zhao, Yu Yuan, Chunze Zhang, Tao He, Changliang Shan, Xiangling Wang, Shuai Zhang","doi":"10.1186/s12575-026-00342-4","DOIUrl":"10.1186/s12575-026-00342-4","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a prevalent and highly lethal malignancy characterized by frequent recurrence and high mortality. 4-Hydroxychalcone (4HC), a common chalcone abundant in daily foods, exhibits multiple biomedical properties, notably anticancer activities. However, the role of 4HC in CRC remains unclear.</p><p><strong>Methods: </strong>Cell proliferation was assessed using cell counting and colony formation assays. Two patient-derived organoid models of CRC and a subcutaneous xenograft model in nude mice treated with 4HC were established to evaluate tumor growth in vivo. Cell cycle distribution, intracellular reactive oxygen species (ROS), DNA damage, and cell senescence were analyzed by flow cytometry, comet assay, SA-β-Gal staining, and western blotting. Molecular docking, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) were performed to determine the interaction between 4HC and CDK6. CDK6 expression in CRC was examined using the TCGA-COAD bulk sequencing dataset and CRC tissue microarrays via immunohistochemistry.</p><p><strong>Results: </strong>We systematically demonstrated that 4HC exerts anticancer effects both in vitro and in vivo. Additionally, 4HC induced cell cycle arrest, promoted ROS accumulation, and triggered DNA damage and cellular senescence in CRC cells. Mechanistically, 4HC exhibited strong binding affinity to CDK6. Furthermore, CDK6 expression was elevated in CRC tissues. Inhibition of CDK6 suppressed cell proliferation, increased ROS production, and induced senescence in CRC cells, whereas the efficacy of 4HC was significantly diminished upon CDK6 silencing.</p><p><strong>Conclusion: </strong>This study demonstrates that 4HC acts as a CDK6 inhibitor, exhibiting potent anticancer effects, and provides a potential novel therapeutic strategy for CRC.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926087","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":"Integrated Genomic and Single-Cell Analysis Identifies Notch1 as a Metastasis Suppressor in Nasopharyngeal Carcinoma Targeted by the AKT/Smad3 Axis.","authors":"Jingjing Zuo, Shiyong Huang, Mengyuan Dai, Fen Li, Ting Huang, Lei Wang, Chenglin Qi, Zezhang Tao, Linfeng Ye","doi":"10.1186/s12575-026-00341-5","DOIUrl":"10.1186/s12575-026-00341-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Notch1 exhibits a high mutation rate in head and neck squamous cell carcinoma (HNSCC), but its functional role in nasopharyngeal carcinoma (NPC) invasion and metastasis remains incompletely understood. This study systematically investigates the function and molecular mechanisms of Notch1 as a metastatic suppressor in NPC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Notch1 expression levels were assessed in NPC tissue microarrays using immunohistochemistry, and correlations with tumor differentiation and metastasis were analyzed. TCGA databases were mined to explore mutation rates and sample clustering based on EMT-related gene signatures. Integrated analysis of TCGA and GEO datasets identified Notch1-associated genes, enabling molecular classification of patients. Additionally, scRNA-seq of NPC clinical samples was performed to validate the association between Notch1, stemness, and EMT features in the tumor microenvironment. The biological functions of Notch1 were further examined in vitro using proliferation (CCK-8, colony formation), migration and invasion (Transwell, wound healing) assays, as well as in vivo xenograft and metastatic models. Molecular mechanisms were probed by examining EMT markers, Smad3 phosphorylation and nuclear translocation, and protein-protein interactions via co-immunoprecipitation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Immunohistochemistry revealed significantly reduced Notch1 expression in NPC tissues, closely associated with poor differentiation and lymph node metastasis. TCGA analysis showed a 16.8% Notch1 mutation rate in HNSCC. Consensus clustering based on EMT-related genes identified subgroups with significant differences in Notch1 mutation status. Using 181 Notch1-related genes from integrated datasets, patients were further classified into three molecular subtypes (C1, C2, C3) with distinct prognosis, Notch1 mutation rates, EMT status, immune landscapes, and ferroptosis-related gene expression. Notably, the C2 subgroup exhibited the highest Notch1 mutation rate, enhanced EMT, poorest prognosis, and immune suppression.Consistent with these multidimensional datasets, scRNA‑seq analysis of primary NPC samples showed that Notch1‑high tumor cells preferentially retained a differentiated epithelial, low‑EMT/low‑stemness phenotype, further supporting an EMT‑ and metastasis‑suppressive role of Notch1 in clinical tumors. Functionally, Notch1 was downregulated across multiple NPC cell lines; knockout of Notch1 significantly promoted NPC cell proliferation, migration, invasion, and EMT both in vitro and in nude mouse models. Mechanistically, Notch1 loss increased EMT marker expression, augmented Smad3 phosphorylation and nuclear translocation, all without altering total Smad3 levels. Notch1 intracellular domain was found to interact directly with Smad3, while AKT and Smad3 interaction decreased upon Notch1 depletion, resulting in elevated Smad3 phosphorylation and EMT gene activation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusi","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761124","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":"Evolutionary Trajectory of Radioresistance in Lung Cancer Brain Metastasis Organoids.","authors":"Jianing Chen, Cize Gao, Li Wang, Leilei Wu, Boyue Pang, Chunxia Su","doi":"10.1186/s12575-026-00339-z","DOIUrl":"10.1186/s12575-026-00339-z","url":null,"abstract":"<p><p>BACKGROUND: Radiotherapy (RT) is a cornerstone treatment for lung cancer brain metastasis (LCBM), yet acquired radioresistance frequently leads to recurrence. The molecular and metabolic mechanisms underlying this adaptive evolution at single-cell resolution remain poorly defined. METHODS: Patient-derived organoids (PDOs) from LCBM tissues were established to model clinical radiation responses. Paired pre- and post-RT samples underwent single-cell RNA sequencing (scRNA-seq) to delineate transcriptional, metabolic, and regulatory alterations associated with radioresistance. RESULTS: Single-cell analysis revealed substantial population remodeling following RT, characterized by depletion of proliferative cells and enrichment of a resilient Hypoxic-EMT subpopulation. Pseudotime analysis demonstrated lineage plasticity, showing a transition from proliferative to mesenchymal states. Mechanistically, a viral mimicry response involving NF-κB and STAT signaling supported stress adaptation. Resistant cells exhibited a hypermetabolic phenotype marked by metabolic plasticity, including hybrid bioenergetics coupling glycolysis with oxidative phosphorylation, enhanced lipid turnover via simultaneous fatty acid synthesis and degradation, and increased glutathione metabolism for reactive oxygen species buffering. Pharmacogenomic profiling indicated concurrent chemotherapy resistance but collateral sensitivity to PI3K/MEK inhibitors and epigenetic therapies. CONCLUSIONS: These findings provide a high-resolution atlas of radioresistance in LCBM and suggest that targeting the Hypoxic-EMT niche or oxidative-antioxidant balance may overcome therapeutic resistance. </p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728256","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}