Biology Direct最新文献

{"title":"Functional genomic imaging (FGI), a virtual tool for visualization of functional gene expression modules in heterogeneous tumor samples.","authors":"Xinlei Chen, Youbing Guo, Xiaorong Gu, Danyi Wen","doi":"10.1186/s13062-025-00598-y","DOIUrl":"10.1186/s13062-025-00598-y","url":null,"abstract":"<p><p>Advances in sequencing technologies are reshaping clinical diagnostics, prompting the development of new software tools to decipher big data. To this end, we developed functional genomic imaging (FGI), a visualization tool designed to assist clinicians in interpreting RNA-Seq results from patient samples. FGI uses weighted gene co-expression network analysis (WGCNA), followed by a modified Phenograph clustering algorithm to identify co-expression gene clusters. These gene modules were annotated and projected onto a t-SNE map for visualization. Annotation of FGI gene clusters revealed three categories: tissue-specific, functional, and positional. These clusters may be used to build tumor subtypes with pre-annotated functions. At the multi-cancer cohort level, tissue-specific clusters are enriched, whereas at the single cancer level, such as in lung cancer or ovarian cancer, positional clusters can be more prominent. Moreover, FGI analysis could also reveal molecular tumor subtypes not documented in clinical records and generated a more detailed co-expression gene cluster map. Based on different levels of FGI modeling, each individual tumor sample can be customized to display various types of information such as tissue origin, molecular subtypes, immune activation status, stromal signaling pathways, cell cycle activity, and potential amplicon regions which can aid in diagnosis and guide treatment decisions. Our results highlight the potential of FGI as a robust visualization tool for personalized medicine in molecular diagnosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"11"},"PeriodicalIF":5.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyltransferase-like 7B participates in bladder cancer via ACSL3 m⁶A modification in a ferroptosis manner.","authors":"Jiani He, Changming Dong, Xiandong Song, Zhongkai Qiu, Hao Zhang, Yuanjun Jiang, Tao Liu, Xiaojun Man","doi":"10.1186/s13062-025-00597-z","DOIUrl":"10.1186/s13062-025-00597-z","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is a malignant tumor. Methyltransferase-like 7B (MEETL7B) is a methyltransferase and its role in BC has not yet been revealed.</p><p><strong>Method: </strong>Stable METTL7B knockdown or overexpression were achieved by lentiviral transduction in SW780 and TCCSUP cell lines. Xenografts tumors were established via subcutaneous injection of stable transfectants in BALB/c mice.</p><p><strong>Results: </strong>A database search indicated that METTL7B was elevated in BC and it was validated in BC cell lines. METTL7B silencing suppressed cell proliferation and tumorigenesis in vitro and in vivo. Besides, METTL7B knockdown induced cell cycle arrest in G1 phase with a reduction in cyclin D1(CCND1), CDK4, and CDK6 levels and an elevation in CDKN2D levels in cells. Considering that ferroptosis is emerging as a therapeutic target for cancer, and the possible relationship between METTL7B and antioxidant enzymes. We, here, examined that ectopic METTL7B expression abolished ferroptosis markers in cells raised by Erastin treatment, including the production of lipid ROS, the increased cellular iron and MDA content, the decreased gene expression of ACSL3, FANCD2, and FADS2, as well as the mitochondrial injury observed by electron microscopy. Mechanically, ectopic METTL7B expression promoted m⁶A modification on ACSL3 mRNA. Gain of functional experiment exhibited that METTL7B inhibited Erastin-induced ferroptosis via ACSL3. Overexpressed PLAGL2 is identified as a possible independent predictor in BC and bioinformatics predicted the potential binding sites between PLAGL2 and METTL7B promoter region. Dual luciferase and chromatin immunoprecipitation analysis provided evidence that PLAGL2 directly binds to METTL7B promoter region.</p><p><strong>Conclusions: </strong>METTL7B is involved in BC development and progression. METTL7B may mediate m⁶A modification on ACSL3 mRNA to negatively regulate ferroptosis in BC cells, which provides a potential therapeutic target for BC via ferroptosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"9"},"PeriodicalIF":5.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix Metalloproteinase-9 is associated with tumor microenvironment remodeling of bladder cancer.","authors":"Fang Fang, Tiange Wu, Mengxue Wang, Wenchao Li, Zonghao You, Ming Chen, Han Guan","doi":"10.1186/s13062-025-00599-x","DOIUrl":"10.1186/s13062-025-00599-x","url":null,"abstract":"<p><p>Tumor microenvironment (TME) takes an essential part in the bladder cancer progression, which is associated with intercellular cross-talk between stroma cells and cancer. We aimed use bioinformatics tools to analyze tumor microenvironment remodeling in bladder cancer. CIBERSORT and ESTIMATE are bioinformatics tools based on deconvolution for calculating proportions of tumor-infiltrating immune cells and stromal components in TME. We utilized these two algorithms to analyze the immune components of 433 bladder cancer cases from The Cancer Genome Atlas database, aiming to compensate for the current lack of large-sample single-cell information. Then we used Cox regression to analyze the prognostic value of differentially expressed genes, and the protein-protein interaction network was constructed. Matrix Metalloproteinase-9 (MMP9) was identified as a predictive biomarker related to immune microenvironment. Using Gene Set Enrichment Analysis, the genes from the group with high MMP9 expression gathered in items related to immune diseases, and genes in the group with low MMP9 expression were negatively associated with valine, leucine and isoleucine degradation and glycosylphosphatidylinositol anchor biosynthesis. MMP9 expression and presence of macrophages M0 were positively correlated, while naïve B cells, activated dendritic cells, monocytes and plasma cells were negatively correlated. The results were confirmed by brightfield and multiplex fluorescence immunohistochemistry using stained bladder cancer and normal tissue.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"8"},"PeriodicalIF":5.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bi-targeting of thioredoxin 1 and telomerase by thiotert promotes cell death of myelodysplastic syndromes and lymphoma.","authors":"Qiangan Jing, Yunyi Wu, Yanchun Li, Chaoting Zhou, Junyu Zhang, Jun Xia, Keyi Li, Yuhuan Shen, Hongfeng Yao, Xiangmin Tong, Jing Du, Lushan Yu, Ying Wang","doi":"10.1186/s13062-025-00594-2","DOIUrl":"10.1186/s13062-025-00594-2","url":null,"abstract":"<p><p>Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal. Mechanistically, our present study revealed that thiotert treatment effectively inhibited the function of the TRX1/TRXR1 system and telomerase reverse transcriptase (TERT), rendering oxidative damage and impairment of telomeres. Meanwhile, pharmacological administration of glutathione (GSH), N-acetylcysteine (NAC), and mitoquinone (MitoQ), or genetic overexpression of TRX1 or TERT in MDS and cells could dampen the toxicity caused by thiotert. Remarkably, the in vivo mouse model of MDS demonstrated that thiotert administration exhibited greater efficacy in tumor reduction compared to the conventional chemotherapy drug cytarabine. Collectively, these results provide experimental insights into the mechanism of thiotert-induced MDS and lymphoma cell death and unveil that thiotert may be an effective and promising new drug for future MDS and lymphoma treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"7"},"PeriodicalIF":5.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated SREBP1 accelerates the initiation and growth of pancreatic cancer by targeting SOX9.","authors":"Cancan Zhou, Zhengyuan Feng, Weikun Qian, Zeen Zhu, Ruiqi Cao, Qiqi Wang, Wunai Zhang, Rujuan Liu, Shuai Wu, Jie Hao, Zheng Wang, Qingyong Ma, Zheng Wu, Xuqi Li","doi":"10.1186/s13062-025-00595-1","DOIUrl":"10.1186/s13062-025-00595-1","url":null,"abstract":"<p><p>Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras^G12D/+;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis. In vitro, either knockdown or pharmacological inhibition of SREBP1 suppressed tumor proliferation but SREBP1 overexpression promoted tumor proliferation. In LSL-Kras^G12D/+;Trp53^fl/+;Pdx1-Cre (KPC) mice, we confirmed the tumor-promoting role of SREBP1 in pancreatic cancer progression. Mechanistically, we revealed SOX9 as a downstream target of SREPB1. SREBP1 inhibition decreased SOX9 expression in both acinar cells and pancreatic cancer cells. Indeed, we identified SREBP1 binding sites in the SOX9 promoter region and reported that SOX9 is transcriptionally regulated by SREBP1. Taken together, our findings demonstrate that SREBP1/SOX9 inhibition suppresses pancreatic cancer initiation and growth, suggesting that SREBP1 could serve as a potential target for cancer screening and treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"6"},"PeriodicalIF":5.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated investigation of mitochondrial genes in COPD reveals the causal effect of NDUFS2 by regulating pulmonary macrophages.","authors":"Xiaoli Zou, Qiqing Huang, Tutu Kang, Shaoran Shen, Chenxi Cao, Jianqing Wu","doi":"10.1186/s13062-025-00593-3","DOIUrl":"10.1186/s13062-025-00593-3","url":null,"abstract":"<p><strong>Background: </strong>Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding of the mitochondrial malfunctions in COPD pathogenesis.</p><p><strong>Results: </strong>Differential expression genes (DEGs) from six publicly available bulk human lung tissue transcriptomic datasets of COPD patients were intersected with the known mitochondria-related genes from MitoCarta3.0 to obtain mitochondria-related DEGs associated with COPD (MitoDEGs). The 32 hub MitoDEGs identified from protein-protein interaction (PPI) networks demonstrated superior overall diagnostic efficacy to non-hub MitoDEGs. Random forest (RF) analysis, least absolute shrinkage and selection operator (LASSO) regression, and Mendelian Randomization (MR) analysis of hub MitoDEGs further nominated NDUFS2, CAT, and MRPL2 as causal MitoDEGs for COPD, whose predominate expressions in pulmonary macrophages were revealed by an independent single-cell transcriptomic dataset of COPD human lungs. Finally, NDUFS2 was evaluated as the top-ranked contributor to COPD in the nomogram model and its downregulation in pulmonary macrophages could result in pro-inflammatory secretion, enhanced intercellular communications, whereas depressed phagocytosis of macrophages as revealed by gene set variation analysis (GSVA) and cell-cell interaction (CCI) analysis of single-cell transcriptomic dataset of COPD human lungs, which was later confirmed in COPD mouse model and macrophage cell lines.</p><p><strong>Conclusions: </strong>Our study established the causal linkage between mitochondrial malfunctions and COPD, providing a potential therapeutic avenue to alleviate pulmonary inflammation accounting for COPD by targeting mitochondria-related genes. NDUFS2, a canonical component of mitochondrial electron respiratory chain, was highlighted instrumental for the susceptibility of risk-exposed individuals to COPD.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"4"},"PeriodicalIF":5.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OSBPL3 modulates the immunosuppressive microenvironment and predicts therapeutic outcomes in pancreatic cancer.","authors":"Qihui Sun, Xiaoqi Zhu, Qi Zou, Yang Chen, Tingting Wen, Tingting Jiang, Xiaojia Li, Fang Wei, Keping Xie, Jia Liu","doi":"10.1186/s13062-025-00596-0","DOIUrl":"10.1186/s13062-025-00596-0","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is characterized by a complex tumor microenvironment that hinders effective immunotherapy. Identifying key factors that regulate the immunosuppressive landscape is crucial for improving treatment strategies.</p><p><strong>Methods: </strong>We constructed a prognostic and risk assessment model for pancreatic cancer using 101 machine learning algorithms, identifying OSBPL3 as a key gene associated with disease progression and prognosis. We integrated multi-dataset analyses, single-cell transcriptomic data, and functional experiments to explore the role of OSBPL3 in pancreatic cancer.</p><p><strong>Results: </strong>Our risk prediction model, developed using machine learning algorithms, demonstrated high predictive accuracy across multiple datasets. Notably, the \"rf\" algorithm model showed an AUC of 1 in the training set and AUCs of 0.887 and 0.977 in two validation datasets. Ridge regression analysis identified OSBPL3 as a core prognostic feature gene. High OSBPL3 expression in pancreatic cancer samples was associated with immunosuppressive characteristics, including reduced CD8 + T cell infiltration and increased immunosuppressive cell populations such as Treg cells and M2 macrophages. Transcriptomic sequencing following OSBPL3 knockdown revealed enrichment of immune-related pathways, suggesting OSBPL3's influence on the immune microenvironment. Single-cell analyses further confirmed OSBPL3's role in shaping the immunosuppressive landscape by modulating Treg cells and M2 macrophages. Additionally, OSBPL3 expression was linked to resistance to immunotherapy, with high OSBPL3 expression associated with lower Immunophenoscore (IPS) scores, indicating poor responsiveness to immunotherapy.</p><p><strong>Conclusions: </strong>Our study reveals OSBPL3 as a critical regulator of the immunosuppressive microenvironment in pancreatic cancer and a potential therapeutic target. Targeting OSBPL3 may enhance the efficacy of immunotherapy and improve patient outcomes. Further research is warranted to explore OSBPL3 as a biomarker for predicting immunotherapy response and as a potential therapeutic target in combination with anti-PD1 therapy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"5"},"PeriodicalIF":5.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of endothelial cell-related gene COL1A1 in prostate cancer diagnosis and immunotherapy: insights from machine learning and single-cell analysis.","authors":"Gujun Cong, Jingjing Shao, Feng Xiao, Haixia Zhu, Peipei Kang","doi":"10.1186/s13062-024-00591-x","DOIUrl":"10.1186/s13062-024-00591-x","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cells are integral components of the tumor microenvironment and play a multifaceted role in tumor immunotherapy. Targeting endothelial cells and related signaling pathways can improve the effectiveness of immunotherapy by normalizing tumor blood vessels and promoting immune cell infiltration. However, to date, there have been no comprehensive studies analyzing the role of endothelial cells in the diagnosis and treatment of prostate adenocarcinoma (PRAD).</p><p><strong>Method: </strong>By integrating clinical and transcriptomic data from TCGA-PRAD, we initially identified key endothelial cell-related genes in PRAD samples through single-cell analysis. Subsequently, cluster analysis was employed to classify PRAD samples based on the expression of these endothelial cell-related genes, allowing us to explore their correlation with patient prognosis and immunotherapy outcomes. A diagnostic model was then constructed and validated using a combination of 108 machine learning algorithms. The XGBoost and Random Forest algorithms highlighted the significant role of COL1A1, and we further analyzed the expression and correlation of COL1A1, AR, and EGFR through multiplex immunofluorescence staining. In vitro experimental analysis of the impact of COL1A1 on the progression of PRAD.</p><p><strong>Results: </strong>Single-cell analysis identified 12 differential prognostic genes associated with endothelial cells. Cluster analysis confirmed a strong correlation between endothelial cell-related genes and both prostate cancer prognosis and immunotherapy responses. Diagnostic models developed using various machine learning techniques demonstrated the significant predictive capability of these 12 genes in the diagnosis of prostate cancer. Furthermore, based on patients' prognostic information, multiple machine learning analyses highlighted the critical role of COL1A1. Immunofluorescence analysis results confirmed that COL1A1 is highly expressed in prostate cancer and is positively correlated with both AR and EGFR. In vitro experiments confirm that reducing COL1A1 expression levels can inhibit PRAD progression.</p><p><strong>Conclusion: </strong>This study provides a comprehensive analysis of the role of endothelial cell-related genes in the diagnosis, prognosis, and immunotherapy of prostate cancer. The findings, supported by various machine learning algorithms and experimental results, highlight COL1A1 as a significant target for the diagnosis and immunotherapy of PRAD.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"3"},"PeriodicalIF":5.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.","authors":"Jin-Xing Wang, Ling Zhang, Peng-Wei Zhang, Luo-Wei Yuan, Jian Jiang, Xiao-Hui Cheng, Wei Zhu, Yong Lei, Fa-Qing Tian","doi":"10.1186/s13062-024-00590-y","DOIUrl":"https://doi.org/10.1186/s13062-024-00590-y","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.</p><p><strong>Methods: </strong>BTZ-resistant cells were generated over a period of at least 6 months by gradually increasing the concentration of BTZ. The viability of MM cell lines and patient bone marrow mononuclear cells (BMMCs) was measured via the CCK8 reagent. The protein levels of cleaved caspase 3, cleaved caspase 7, cleaved PARP, PARP, p-JNK, JNK, and γ-H2AX were analyzed through Western blot. Cellular morphology was observed via transmission electron microscopy. Colony formation ability was evaluated, and cell apoptosis and the cell cycle were detected through flow cytometry. Xenograft experiments were conducted to evaluate the growth of MM cells in vivo.</p><p><strong>Results: </strong>Our results demonstrated that boanmycin effectively inhibited cell proliferation and colony formation, and triggered apoptosis in both BTZ-sensitive and BTZ-resistant MM cells. The combination of boanmycin with BTZ had greater inhibitory effects than either drug alone. Furthermore, boanmycin significantly suppressed MM cell growth in immunodeficient mouse xenograft models without inducing distinct toxic side effects. Notably, boanmycin markedly killed patient-derived MM cells ex vivo. Mechanistically, boanmycin not only disrupts the cell cycle and causes DNA damage but also exerts its antitumor effects by inducing endoplasmic reticulum (ER) functional impairment.</p><p><strong>Conclusions: </strong>Our findings highlight the potential of boanmycin as a promising novel therapeutic option for treating MM, particularly in patients with BTZ resistance.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"1"},"PeriodicalIF":5.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing liquid-liquid biopolymer regulators to predict the prognosis and drug sensitivity of hepatocellular carcinoma.","authors":"Jianhao Li, Han Chen, Lang Bai, Hong Tang","doi":"10.1186/s13062-025-00592-4","DOIUrl":"https://doi.org/10.1186/s13062-025-00592-4","url":null,"abstract":"<p><strong>Background: </strong>Liquid-liquid phase separation (LLPS) is essential for the formation of membraneless organelles and significantly influences cellular compartmentalization, chromatin remodeling, and gene regulation. Previous research has highlighted the critical function of liquid-liquid biopolymers in the development of hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This study conducted a comprehensive review of 3,685 liquid-liquid biopolymer regulators, leading to the development of a LLPS related Prognostic Risk Score (LPRS) for HCC through bootstrap-based univariate Cox, Random Survival Forest (RSF), and LASSO analyses. A prognostic nomogram for HCC patients was developed using LPRS and other clinicopathological factors. We utilized SurvSHAP to identify key genes within the LPRS influencing HCC prognosis. To validate our findings, we collected 49 HCC cases along with adjacent tissue samples and confirmed the correlation between DCAF13 expression and HCC progression through qRT-PCR analysis and in vitro experiments.</p><p><strong>Results: </strong>LPRS was established with 8 LLPS-related genes (TXN, CBX2, DCAF13, SLC2A1, KPNA2, FTCD, MAPT, and SAC3D1). Further research indicated that a high LPRS is closely associated with vascular invasion, histological grade (G3-G4), and TNM stage (III-IV) in HCC, concurrently establishing LPRS as an independent risk factor for prognosis. A nomogram that integrates LPRS with TNM staging and patient age markedly improves the predictive accuracy of survival outcomes for HCC patients. Our findings suggest that increased DCAF13 expression in HCC plays a crucial role in cancer progression and angiogenesis. Navitoclax has emerged as a promising treatment for HCC patients with high LPRS levels, offering a novel therapeutic direction by targeting LLPS.</p><p><strong>Conclusion: </strong>We have formulated a novel LPRS model that is capable of accurately predicting the clinical prognosis and drug sensitivity of HCC. DCAF13 might play a pivotal role in malignant progression mediated by LLPS.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"2"},"PeriodicalIF":5.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}