FASEB bioAdvances最新文献

{"title":"Single-Cell RNA Sequencing Reveals the Critical Role of SEC16B in Lung Metastasis of Osteosarcoma","authors":"Shangyu Liu,&nbsp;Haijun Tang,&nbsp;Shanhang Li,&nbsp;Jian Guan,&nbsp;Yangjie Cai,&nbsp;Hening Li,&nbsp;Weijie Yan,&nbsp;Wei Dai,&nbsp;Danting Xiao,&nbsp;Zhuan Zou,&nbsp;Wenyu Feng,&nbsp;Xinli Zhan,&nbsp;Yun Liu,&nbsp;Juliang He","doi":"10.1096/fba.2024-00161","DOIUrl":"https://doi.org/10.1096/fba.2024-00161","url":null,"abstract":"<p>Osteosarcoma (OS) is highly malignant and easily prone to lung metastasis. The mechanisms of lung metastasis in OS remain unclear. The single-cell RNA sequencing (scRNA-seq) samples in this study included six primary osteosarcoma samples (published in-house data), two lung metastasis samples (GSE152048), and four normal bone tissue samples (GSE169396). To identify potential targets for metastasis, bulk RNA sequencing data from four primary tumors and four lung metastases (in-house data) were also analyzed. scRNA-seq identified five tumor cell subpopulations. CytoTRACE and lung metastasis scores indicated that the C1 subpopulation was most closely associated with lung metastasis. By intersecting lung metastasis-related genes identified via hdWGCNA analysis with differentially expressed genes from bulk RNA sequencing, <i>SEC16B</i> was identified as the key gene influencing lung metastasis. qRT-PCR results revealed that <i>SEC16B</i> expression was significantly downregulated in OS cell lines. Transwell assay demonstrated that overexpression of <i>SEC16B</i> significantly inhibited the invasion and migration capabilities of OS cells. Additionally, analyses using Scissor, CellphoneDB, and CSOmap suggested that fibroblasts, endothelial cells, and OS cells in the tumor microenvironment formed a pre-metastatic niche through mechanisms involving angiogenesis and extracellular matrix remodeling. Overall, this study identifies a new population that may promote lung metastasis by downregulating <i>SEC16B</i> in OS. Moreover, fibroblasts and endothelial cells in the tumor microenvironment play a critical role in OS lung metastasis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"A. Rabeling,&nbsp;M. Goolam","doi":"10.1096/fba.70040","DOIUrl":"https://doi.org/10.1096/fba.70040","url":null,"abstract":"<p><b>Cover image caption:</b> Cover image adapted from “Signaling Centers Drive Brachyury Dynamics and Lineage Commitment in mESC Aggregates” by Rabeling and Goolam (10.1096/fba.2024-00131). \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix Stiffness Regulates TGFβ1-Induced αSMA Expression via a G9a-LATS-YAP Signaling Cascade","authors":"Chinmay S. Sankhe,&nbsp;Jessica L. Sacco,&nbsp;Victoria L. Crunkleton,&nbsp;Malcom Díaz García,&nbsp;Matthew J. Bierowski,&nbsp;David Vidotto Rezende Soares,&nbsp;Jacob A. Karnick,&nbsp;Rachel L. Cecco,&nbsp;Arefeh Abbasi,&nbsp;Joy Kirigo,&nbsp;Thomas K. Wood,&nbsp;Esther W. Gomez","doi":"10.1096/fba.2025-00117","DOIUrl":"https://doi.org/10.1096/fba.2025-00117","url":null,"abstract":"<p>Extracellular matrix stiffness is enhanced in cancer and fibrosis; however, there is limited knowledge on how matrix mechanics modulate expression and signaling of the methyltransferase G9a. Here, we show that matrix stiffness and transforming growth factor (TGF)-β1 signaling together regulate G9a expression and the levels of the histone mark H3K9me2. Suppressing the activity and expression of G9a attenuates TGFβ1-induced alpha smooth muscle actin (αSMA) and N-cadherin expression and cell morphology changes in mammary epithelial cells cultured on stiff substrata. Knockdown of G9a increases the expression of large tumor suppressor kinase 2 (LATS2) and decreases the nuclear localization of yes associated protein (YAP). Furthermore, inhibition of LATS promotes an increase in YAP nuclear localization and αSMA expression, while inhibition of YAP attenuates αSMA expression. Overall, our findings indicate that a G9a-LATS-YAP signaling cascade regulates mammary epithelial cell response to matrix stiffness and TGFβ1.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PICRUSt2 Analysis of Fecal Microbiome Associated With a Murine Model of Multiple Sclerosis","authors":"Sean M. Schumacher,&nbsp;William J. Doyle,&nbsp;Kristina Hill,&nbsp;Javier Ochoa-Repáraz","doi":"10.1096/fba.2025-00060","DOIUrl":"https://doi.org/10.1096/fba.2025-00060","url":null,"abstract":"<p>Multiple sclerosis (MS) is a debilitating neuroinflammatory disease of the central nervous system (CNS). Approximately 2–3 million people globally are believed to have MS. There is growing interest in the mechanistic link between MS and gut microbiome composition. Experimental autoimmune encephalomyelitis (EAE) is a murine model of inflammatory demyelination of the CNS commonly used to investigate the pathology of MS in relation to the microbiome. Previous research has shown that EAE affects the gut microbiome, and the improvement of EAE can promote microbiome homeostasis. Microbiome homeostasis is crucial for host health, as it contributes to immune regulation and produces bioavailable metabolic products in the digestive tract. Several factors, including diet, genetics, and environment, influence microbiome homeostasis apart from disease state. Our lab previously demonstrated that mice of the same genetic line, sourced from different manufacturers, exhibit differences in microbiome composition despite being housed under similar conditions. Furthermore, these mice showed variations in EAE progression and severity, indicating that differences in the microbiome may contribute to the discrepancies in EAE. Here, we employ PICRUSt2 to estimate functional differences in the microbiomes of EAE mice from various sources at key time points during the EAE disease course. The reanalysis of our microbiome data reveals distinct differences in predicted gene expression of microbiomes that are disproportionately related to the metabolism of amino acids, carbohydrates, lipids, and other metabolites. Our findings support previous observations regarding microbiome alterations in the context of EAE and suggest that evaluating microbiome dynamics would benefit from both taxonomic assessment and metabolic activity, allowing for more effective and comprehensive research strategies.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Inflammatory Proteins Mediate the Causal Effect of Gut Microbiota on Inflammatory Bowel Disease: Bayesian and Mediated Mendelian Randomization","authors":"Zeyang Li,&nbsp;Lei Jia,&nbsp;Shengnan Huai","doi":"10.1096/fba.2025-00114","DOIUrl":"https://doi.org/10.1096/fba.2025-00114","url":null,"abstract":"<p>Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents a global public health challenge. Although the relationships between gut microbiota, inflammatory proteins, and IBD are recognized, their causal associations and mediating roles remain unclear. Large-scale genome-wide association study data on 473 gut microbiota, 91 circulating inflammatory proteins, and IBD (including CD and UC) were analyzed. Univariable Mendelian randomization (UVMR), Bayesian Weighted MR (BWMR), mediation MR, and sensitivity analyses were used to explore causal associations and quantify mediating effects. MR results indicate that 24, 20, and 22 gut microbiota exhibit causal effects on IBD (nine protective factors, 15 risk factors), CD (nine protective factors, 11 risk factors) and UC (seven protective factors, 15 risk factors). Three inflammatory proteins (one protective factors, two risk factors) have causal effects on IBD, with five having causal effects on CD (one protective factors, four risk factors) and UC (two protective factors, three risk factors). Mediation analysis reveals that Interleukin-17C levels mediate the causal effects of <i>Acetobacterales</i> and <i>Bifidobacterium</i> on IBD. T-cell surface glycoprotein CD6 isoform levels mediate the causal effect of <i>Faecalibacterium prausnitzii E</i> on CD. Interleukin-17C levels also mediate the causal effects of <i>Acetobacterales</i> on UC and <i>Phocea massiliensis</i> on UC. Gut microbiota and circulating inflammatory proteins play key roles in IBD pathogenesis, with Interleukin-17C and T-cell surface glycoprotein CD6 identified as key intermediates in the causal pathway. These findings provide novel biomarkers and potential therapeutic targets for preventing and treating IBD, CD, and UC.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PINK1 Loss of Function Selectively Alters the Mitochondrial-Derived Vesicle Pathway","authors":"Charlotte L. Collier,&nbsp;Colleen Ruedi,&nbsp;Naomi J. Thorne,&nbsp;David A. Tumbarello","doi":"10.1096/fba.2024-00200","DOIUrl":"https://doi.org/10.1096/fba.2024-00200","url":null,"abstract":"<p>Cell homeostasis and metabolic control require the efficient function of mitochondria and implementation of quality control pathways following damage. Cells have various discrete pathways of mitochondrial quality control (mitoQC) to maintain the healthy network. PINK1 and Parkin are two key players in mitoQC, most highly associated with the ubiquitin-dependent capture and degradation of whole mitochondria by autophagy. However, these proteins have alternative roles in repair routes directing locally damaged cargo to the lysosome, such as the mitochondrial-derived vesicle (MDV) pathway. We aimed to clarify the role of PINK1 and determine how its loss of function impacts mitochondrial dynamics and quality control. Results indicate PINK1 knockout (KO) has little impact on whole mitochondrial turnover in response to damage in SH-SY5Y cells, whereas both PINK1 and Parkin KO cells have healthy mitochondrial networks with efficient ATP production. However, TOM20 positive outer-membrane and damage-induced PDH-positive inner-membrane MDVs are elevated in PINK1 KO cells. Although, in contrast to Parkin KO, this is not due to a defect in trafficking to a LAMP1-positive compartment and may instead indicate increased damage-induced flux. In comparison, loss of Atg5-dependent mitophagy has no effect on whole mitochondrial turnover and only results in a limited elevation in inner-membrane MDVs in response to damage, indicating autophagy-independent mechanisms of whole mitochondrial turnover and a minor compensatory increase in damage-induced MDVs. Therefore, these data suggest PINK1 and Parkin are dispensable for whole mitochondrial turnover, but following their perturbation have disparate effects on the MDV pathway.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers","authors":"Lorenzo Sanesi,&nbsp;Roberta Zerlotin,&nbsp;Alessio Campiolo,&nbsp;Angela Oranger,&nbsp;Manuela Dicarlo,&nbsp;Clelia Suriano,&nbsp;Ameneh Ghadiri,&nbsp;Graziana Colaianni,&nbsp;Maria Grano,&nbsp;Sara Tavella,&nbsp;Silvia Colucci","doi":"10.1096/fba.2025-00085","DOIUrl":"https://doi.org/10.1096/fba.2025-00085","url":null,"abstract":"<p>Microgravity exposure affects both tissues and cells, and, in this regard, one of the most affected targets is the skeletal muscle system due to the significant loss of bone and muscle mass leading to osteoporosis and sarcopenia, respectively. Several efforts are underway to counteract the effects of microgravity, and recent studies on irisin, a myokine with anabolic effects on the musculoskeletal system, have shown promising results. Due to the practical challenges of conducting experiments in actual microgravity, different devices generating a simulated microgravity condition on Earth have been developed. Here, we exposed myoblasts, osteoblasts, osteocytes to a random position machine (RPM) for five days to assess microgravity effect on the expression of key differentiation factors in cells untreated or treated with irisin. In myoblasts (C2C12), exposure to RPM led to increased expression of early myogenesis maker genes <i>Pax7</i> (<i>p</i> = 0.0016), <i>Myf5</i> (<i>p</i> = 0.0005) and <i>MyoD</i> (<i>p</i> = 0.0009). Irisin treatment in the last 8 h of RPM cultures prevented these increases by returning <i>Pax7</i> (<i>p</i> = 0.0008) and <i>MyoD</i> (<i>p</i> = 0.01) to control values, and only partially <i>Myf5</i>. In bone cells, exposure to RPM for 5 days showed no effect in osteoblasts (MC3T3) but decreased the expression of <i>Pdpn</i> (<i>p</i> = 0.0285) and <i>Dmp-1</i> (<i>p</i> = 0.0423) genes in osteocytes (MLO-Y4). Irisin treatment completely prevented the decline in <i>Pdpn</i> (<i>p</i> = 0.293) and <i>Dmp-1</i> (<i>p</i> = 0.0339) levels. Overall, our data showed that the impact of RPM exposure keeps myoblasts and osteocytes in a proliferative state, and irisin treatment restores them to their baseline biological condition, suggesting that irisin can counteract the changes induced by simulated microgravity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Inflammation in Migraine Headaches: A Review","authors":"Caryn T. Morgan,&nbsp;Sanah M. Nkadimeng","doi":"10.1096/fba.2024-00188","DOIUrl":"https://doi.org/10.1096/fba.2024-00188","url":null,"abstract":"<p>Migraine is a chronic pulsating primary headache affecting billions of individuals worldwide. The condition is associated with neuroinflammation and is listed as the second most common form of headache disorders and the leading cause of disabilities. Migraineurs are susceptible to various pathological conditions ranging from mood and emotional dysregulation to neuronal disorders. Consequently, they often experience a higher rate of depression compared to non-migraineurs. Some migraineurs do not respond effectively to conventional drugs. As a result, there is a need for more alternative, effective treatment plans. Understanding the role of inflammation in migraine headache conditions could potentially bring solutions. The aim of the review is to outline the role of inflammation, focusing on neuronal excitability, pain, and inflammatory pathways involved in the context of migraine headaches. With the use of various academic and research databases, articles linked to inflammation and neuroinflammation were considered. Data were collected and analyzed surrounding inflammatory biomarkers and their link to migraine pathophysiology and current treatment plans. Studies highlight the impact of inflammatory mediators and neurotransmitters like interleukins (IL-1<i>β</i>,6,8,10), tumor necrosis factor-alpha (TNF-<i>α</i>), transforming growth-factor-beta (TNF-<i>β</i>), glutamate, and chemokines in the onset and severity of migraine headaches with and without aura, eliciting pain and inflammatory responses in the central nervous system. Studies also linked migraines and mood disorders, contributing to the increase in comorbidity prevalence. Further research is needed to address the increasing burden and gaps in existing treatments surrounding the inadequate relief and side effects reported with some migraine treatments. In addition, the use of medicinal plants for inflammation-targeted therapy needs to be further explored for more viable alternative treatments.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic Reticulum Stress and Unfolded Protein Response Sensor ERN1 Regulates Organic Dust Induction of Lung Inflammation","authors":"Shilpa Kusampudi,&nbsp;Velmurugan Meganathan,&nbsp;Vijay Boggaram","doi":"10.1096/fba.2025-00069","DOIUrl":"https://doi.org/10.1096/fba.2025-00069","url":null,"abstract":"<p>Inhalation of organic dust increases the risk for respiratory symptoms and respiratory diseases, with chronic inflammation playing a major role in their development. Previously, we reported that organic dust induction of inflammatory mediators in bronchial epithelial cells is mediated through increase of intracellular reactive oxygen species (ROS) and activation of NFκB and Stat3. Oxidative stress caused by increased ROS has been linked to the activation of endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR modulates immune responses and plays key roles in the development of acute and chronic diseases. Herein, we hypothesized that organic dust-induced ER stress-UPR regulates airway epithelial cell inflammatory responses. We found that poultry organic dust extract (referred to as dust extract) increased the expression of ER stress/UPR sensor ERN1 in Beas2B bronchial epithelial cells. Dust extract was also found to increase ERN1 protein levels in mouse lungs with ERN1 immunostaining detected predominantly in the bronchial epithelium. Additionally, dust extract increased Ser724 ERN1 phosphorylation in the mouse bronchial epithelium indicating activation. Chemical inhibition and mRNA knockdown studies revealed that TLR2/TLR4-Myd88-ROS-NFκB/Stat3 pathway mediates ERN1 induction. ERN1 chemical inhibitors, KIRA6 and APY29, and ERN1 mRNA knockdown reduced the induction of IL6, CXCL8, and pro IL1β. KIRA6 inhibited dust extract stimulation of NFκB-p65, Stat3, Jun and MAPK 8/9 phosphorylation. Our studies have shown that ER stress and ERN1 are new players in the control of organic dust induced lung inflammation. Cross-regulation between members of cell signaling cascade, TLR2-TLR4/MyD88/ROS/ERN1/NFκB/Stat3 may fine tune immune and inflammatory responses elicited by organic dust.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of TBC1D1 and Its Relationship With the Tumor Microenvironment in Pancreatic Cancer: A Study Based on Single-Cell Sequencing","authors":"Linfeng Yang,&nbsp;Duan Yan,&nbsp;Jun Yu,&nbsp;Dawei Deng,&nbsp;Lin Ma,&nbsp;Ruixin Yu,&nbsp;Song Wei,&nbsp;Jiahui Yu,&nbsp;Chuan Lan,&nbsp;Pengsheng Yi","doi":"10.1096/fba.2025-00092","DOIUrl":"https://doi.org/10.1096/fba.2025-00092","url":null,"abstract":"<p>TBC1 Domain Family Member 1 (TBC1D1) plays a crucial role in various cancers. However, its specific function in pancreatic cancer (PC) remains poorly understood. In this study, we aimed to evaluate the prognostic value of TBC1D1 and its correlation with the tumor microenvironment (TME) in PC. A total of 168 patients with PC were included in this study. The expression of TBC1D1 in patients was detected by immunohistochemistry. Additionally, single-cell RNA sequencing (scRNA-seq) was used to reveal the expression distribution and proportion of TBC1D1 across different cell populations. The relationship between TBC1D1 expression levels and the TME was further explored based on high and low TBC1D1 expression groups. Multivariate analysis revealed that TBC1D1 positivity was an independent adverse prognostic factor for overall survival (OS; <i>p</i> = 0.026). Immunohistochemistry and single-cell RNA sequencing analyses revealed that TBC1D1 expression was positively correlated with fibroblast activation protein, programmed cell death protein 1, and programmed cell death ligand-1 positivity but negatively correlated with clusters of differentiation 8T cells positivity. Our findings revealed that TBC1D1 is an independent prognostic risk factor in patients with PC and may promote PC progression by modulating the TME.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}