FASEB bioAdvances最新文献

{"title":"XIST Is a Key Modulator Associated With the Adhesome Network","authors":"Dongning Chen,&nbsp;Nolan Origer,&nbsp;Sha Sun,&nbsp;Timothy L. Downing","doi":"10.1096/fba.2026-00185","DOIUrl":"https://doi.org/10.1096/fba.2026-00185","url":null,"abstract":"<p>A long non-coding RNA (lncRNA) known as the X-inactivation specific transcript (<i>XIST</i>) plays a central role in X chromosome inactivation—a transcriptional process that silences one of the two X chromosomes in females to ensure dosage compensation between males and females. Much research has been conducted on how <i>XIST</i> regulates X chromosome transcription critical to embryonic development, but recent studies suggest a non-canonical role for <i>XIST</i> in regulating cancer stem cells and cellular plasticity. As cell adhesion and adhesome genes are integral to the regulation of cancer stemness, we explored the previously unrecognized link between <i>XIST</i> and the adhesome network. By performing gene expression and gene ontology analysis on <i>XIST</i>-knockdown ovarian cancer cells, our study showed that <i>XIST</i> loss altered adhesome gene expression and downstream adhesion pathways. Using Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets, we identified distinct correlations between <i>XIST</i> lncRNA and adhesome genes across normal and cancer tissue samples, which are associated with cell stemness. Furthermore, network analysis suggests that <i>XIST</i> may interact with specific adhesome genes within the cell nucleus. This interaction may have significant functional implications, as demonstrated by the hazard ratio analysis of <i>XIST</i> and adhesome gene expression in relation to clinical outcomes. Overall, our results show that among well-annotated functional lncRNAs, <i>XIST</i> appears to be a modulator strongly associated with the adhesome network and cell stemness. Our findings thus support a novel link between lncRNA-mediated epigenetic regulation of cell adhesion genes, highlighting <i>XIST</i> as a key regulator contributing to the adhesome network.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994614","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":"Glial and Vascular Plasma Biomarkers Across the Alzheimer's Disease Continuum: An ADNI-Based Longitudinal Study","authors":"Khodakaram Jahanbin,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1096/fba.2026-00194","DOIUrl":"https://doi.org/10.1096/fba.2026-00194","url":null,"abstract":"<p>Alzheimer's disease (AD) is increasingly recognized as a multicellular disorder involving neurovascular unit dysfunction. Investigating glial and vascular biomarkers together may provide a more integrated view of AD biology. This study characterized baseline distributions, interrelationships, and longitudinal trajectories of plasma glial (GFAP, sTREM2) and vascular/endothelial (VEGF, sICAM-1, sVCAM-1) biomarkers across the AD continuum. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) data, this retrospective longitudinal cohort study included a covariate-complete clinical cohort of 2650 participants classified as cognitively unimpaired (CU), mild cognitive impairment (MCI), or AD dementia. Biomarker-specific analytic samples were determined by assay availability and complete-case requirements. Associations were evaluated using covariate-adjusted linear regression and linear mixed-effects models with participant random intercepts, adjusted for baseline age, sex, education, and APOE ε4 status. Vascular models were additionally refitted with body mass index, systolic blood pressure, antihypertensive and antidiabetic medication use, smoking history, and estimated glomerular filtration rate. Baseline GFAP showed a robust stepwise elevation from CU to MCI to AD (56.3% higher in AD than CU, <i>q</i> = 1.7 × 10⁻¹⁴; area under the curve 0.82), whereas sTREM2 distributions overlapped across groups. VEGF and sVCAM-1 were higher in AD than CU (14.1%, <i>q</i> = 0.014; 14.7%, <i>q</i> = 0.002), with areas under the curve of 0.61 and 0.63 and more than 80% distribution overlap. GFAP increased by 4.50% per year in CU participants and sTREM2 by 2.99% per year, with no significant diagnosis-by-time interactions for either. Over a 12-month interval, sICAM-1 declined in CU participants, and this decline was attenuated in MCI and AD, while sVCAM-1 increased in CU participants and showed negative diagnosis-by-time interactions. The vascular longitudinal findings were unchanged by adjustment for cardiometabolic and renal covariates, by time-varying diagnosis, and by separating stable MCI from MCI-to-AD converters. Correlations among vascular markers were consistent and well estimated, whereas glial-vascular correlations were based on 64 to 94 overlapping participants and were not significant. Glial and vascular plasma biomarkers did not progress synchronously across the AD continuum. GFAP showed the strongest and most discriminating diagnosis-associated elevation. Vascular markers showed statistically robust but small group-level differences with no individual-level discriminative utility, and their divergent 12-month trajectories require replication over longer follow-up before they can be interpreted as stage-dependent regulation.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994253","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 Human PNPLA3I148M Polymorphism Alters the Renal Kinome and Transporters to Cause Hyperfiltration and Hypertension","authors":"Gertrude Arthur,&nbsp;Michael I. Adenawoola,&nbsp;Sally Wahba,&nbsp;Bentley S. Montgomery,&nbsp;Claire B. Wingfield,&nbsp;Zachary A. Kipp,&nbsp;Terry D. Hinds Jr.,&nbsp;David E. Stec","doi":"10.1096/fba.2026-00222","DOIUrl":"https://doi.org/10.1096/fba.2026-00222","url":null,"abstract":"<p>The patatin-like phospholipase domain-containing protein 3 (Pnpla3) I148M polymorphism is a well-established genetic determinant of metabolic dysfunction-associated steatotic liver disease (MASLD), and emerging evidence links it to chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the mechanisms underlying this relationship remain unclear. The goal of this study was to investigate the role of the Pnpla3^I148M polymorphism on kidney function, blood pressure, and cardiac function in a mouse model carrying the identical human polymorphism. Male and female Pnpla3^I148M knock-in and control C57BL/6 mice were fed either a normal sucrose diet (NSD) or a high sucrose diet (HSD) for 8 weeks. Glomerular filtration rate (GFR), blood pressure, cardiac, and vascular function were measured in each group. Renal cortical protein expression and kinome profiles were analyzed to identify pathways associated with hyperfiltration and renal injury. Pnpla3^I148M mice exhibited increased renal sodium transporter levels and hyperfiltration, which was compounded by albuminuria in HSD mice. Pnpla3^I148M mice were also hypertensive and exhibited impaired systolic function, consistent with pressure-overload-induced cardiac remodeling. Renal kinome profiling revealed sex- and diet-dependent alterations in serine/threonine kinases, primarily involving isoforms of protein kinase C (PKC), protein kinase A (PKA), cGMP-dependent protein kinase (PRKG), and calcium/calmodulin-dependent protein kinase (CaMK). Our findings suggest that Pnpla3^I148M acts as a systemic cardio-renal risk allele that links metabolic dysregulation to progressive end-organ damage via renal kinase remodeling in a sex- and diet-dependent manner.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994615","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":"MicroRNA-Mediated Placental Maladaptation in Preeclampsia Pathogenesis","authors":"Sarbani Saha,&nbsp;Rupasri Ain","doi":"10.1096/fba.2026-00062","DOIUrl":"10.1096/fba.2026-00062","url":null,"abstract":"<p>Preeclampsia (PE) is a pregnancy-specific disorder characterized by maternal hypertension and proteinuria, typically manifesting in the late second or third trimester. It affects approximately 5%–8% of pregnancies worldwide and accounts for nearly 10%–15% of maternal deaths. PE is also associated with adverse neonatal outcomes, including preterm birth, fetal growth restriction, and low birth weight, with long-term cardiovascular and metabolic consequences for both mother and offspring. Although clinical symptoms appear in the latter half of pregnancy, substantial evidence indicates that PE originates earlier during placental development. Impaired trophoblast invasion and defective spiral artery remodeling result in placental insufficiency, compromised uteroplacental perfusion, and a hypoxic placental microenvironment, which are hallmark features of the disease. Despite extensive research, PE remains a heterogeneous disorder lacking reliable early diagnostic markers or effective targeted therapies, with placental delivery remaining the only definitive treatment. MicroRNAs (miRNAs) have emerged as critical regulators of placental development and function. Owing to their abundance, evolutionary conservation, and ability to modulate multiple gene networks, miRNAs regulate trophoblast proliferation, migration, invasion, angiogenesis, and apoptosis, processes that are profoundly disrupted in PE. Genome-wide expression studies have revealed widespread dysregulation of placental miRNAs in PE, frequently associated with hypoxia and angiogenic imbalance. This review summarizes current advances in miRNA expression and function in the preeclamptic placenta, focusing on their roles in trophoblast dysfunction and disease pathogenesis. We highlight differentially expressed placental miRNAs, their targets, and the regulatory pathways they influence, emphasizing the central role of miRNA-mediated gene regulation in the development and progression of PE.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988334","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":"Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet","authors":"Praghalathan Kanthakumar,&nbsp;Adebowale Adebiyi","doi":"10.1096/fba.2026-00066","DOIUrl":"10.1096/fba.2026-00066","url":null,"abstract":"<p>Urotensin II (UII) signaling through its Gq-coupled receptor (UT) has been implicated in metabolic and vascular dysfunction; however, its contribution to diabetic kidney disease (DKD) and renal lipid remodeling remains incompletely defined. We examined kidney injury and lipidomic alterations in wild-type (WT) and UT knockout (UT KO) mice fed a long-term high-fat diet (HFD). Male WT and UT KO mice were fed HFD (60% kcal fat) or low-fat diet (LFD; 10% kcal fat) for 33 weeks. Despite comparable HFD-induced obesity, hyperglycemia, and hyperinsulinemia, UT deletion significantly attenuated albuminuria, glomerular and tubular fibrosis, histopathologic injury scores, glomerular basement membrane thickening, and podocyte foot process effacement. UT deficiency also reduced systemic and renal markers of endoplasmic reticulum (ER) stress. Untargeted renal lipidomics profiling (1320 lipid species) revealed no genotype-dependent differences under LFD conditions. In contrast, HFD altered 52 lipid species in WT kidneys, prominently affecting phospholipids, glycosphingolipids, ceramides, sphingomyelins, and triglycerides. UT deletion mitigated dysregulation of 41 of these lipid species, indicating that UT signaling promotes maladaptive renal lipid remodeling in DKD. UT expression was confirmed in native and cultured mouse podocytes. In vitro, UII stimulated ER Ca²⁺ release, induced ER stress, and disrupted the actin cytoskeleton in podocytes; these effects were prevented by UT antagonism or inhibition of transient receptor potential canonical 6 channels. Collectively, these findings identify UII–UT signaling as a key mediator of lipid dysregulation and global kidney injury affecting the glomerular filtration barrier, tubules, and interstitium under HFD, supporting UT antagonism as a potential renometabolic therapeutic strategy.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918932","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":"Conditional eIF2A Deletion Suggests Extra-Adipose Mechanisms Underlying Metabolic Syndrome in Total-Body eIF2A Knockout Mice","authors":"Adedeji Isaac Adeloye,&nbsp;Richard Anderson,&nbsp;Anchal Agarwal,&nbsp;Barsanjit Mazumder,&nbsp;Taras Y. Nazarko,&nbsp;Atefeh Bagheri,&nbsp;Archana Prabahar,&nbsp;Peng Jiang,&nbsp;Frank Tedeschi,&nbsp;William C. Merrick,&nbsp;David A. Buchner,&nbsp;Maria Hatzoglou,&nbsp;Roman V. Kondratov,&nbsp;Anton A. Komar","doi":"10.1096/fba.2026-00271","DOIUrl":"10.1096/fba.2026-00271","url":null,"abstract":"<p>Dynamic regulation of protein synthesis is essential for metabolic homeostasis, with translation initiation playing a key role in this process. Emerging evidence strongly indicates that in addition to canonical eukaryotic initiation factors (e.g., eIF2, eIF4E) non-canonical factors, such as eukaryotic initiation factor 2A can modulate metabolic homeostasis. eIF2A is a highly conserved eukaryotic protein originally proposed to function analogously to bacterial IF2, promoting initiator Met-tRNAi recruitment to the 40S ribosomal subunit, though its precise mechanism remains debated. To investigate its organismal role, we have previously generated the total-body eIF2A knockout mouse, which revealed eIF2A functions in lipid homeostasis, glucose tolerance, insulin sensitivity, and susceptibility to metabolic syndrome. To further determine whether adipose tissue drives these phenotypes, we presently generated adipose-specific eIF2A knockout mice. Despite dysregulation of some key adipokines, including for example, adiponectin, these mice did not develop metabolic syndrome, even under high-fat diet conditions, indicating that adipose tissue specific deficiency of eIF2A is insufficient to reproduce the metabolic defects observed in total-body knockout. However, we found that eIF2A deficiency in the liver of the total body eIF2A-KO mice can independently drive metabolic syndrome components via translational control of Lpin1 (a phosphatidate phosphatase and a transcriptional coactivator) that controls hepatic lipid storage and metabolism. eIF2A deficiency in the liver leads to disruption of fatty acid oxidation and the production of ketone bodies, not observed in adipose-specific eIF2A knockout mice. Our findings suggest that systemic metabolic effects observed in the total body eIF2A-KO mice may arise from coordinated functions across multiple organs.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911315","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":"Supraphysiological 25-Hydroxyvitamin D3 and Calcipotriol Induce Reactive Oxygen Species, Mitochondrial Dysfunction and Apoptosis in HeLa Cervical Cancer Cells","authors":"Hoi Ching Cherry Chan,&nbsp;Sachin Bhoora,&nbsp;Esther Zhou,&nbsp;Sumari Marais,&nbsp;Tahir S. Pillay,&nbsp;Rivak Punchoo","doi":"10.1096/fba.2026-00063","DOIUrl":"https://doi.org/10.1096/fba.2026-00063","url":null,"abstract":"<p>Cervical cancer remains a major global health challenge, necessitating continued advances in therapeutic strategies. Emerging evidence suggests that vitamin D derivatives may exert anti-cancer effects, including induction of apoptosis, potentially through redox-dependent mechanisms. This study investigated whether vitamin D exposure is associated with reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and apoptosis in cervical cancer cells. HeLa cells were exposed to physiological, intermediate, and supraphysiological concentrations of 25-hydroxyvitamin D₃, as well as calcipotriol, a 1,25-dihydroxyvitamin D analogue. Cell viability assays (crystal violet, Alamar Blue, and Muse cell viability) demonstrated dose-dependent reductions in viability. Flow cytometric analyses demonstrated increased apoptotic markers, evidenced by Annexin V binding and caspase-3/7 activation. The oxidative stress assay showed increased ROS-positive cell populations, accompanied by mitochondrial membrane depolarization. Catalase and total superoxide dismutase activities decreased at the highest effective concentrations. In parallel, decreased total expression of proteins within the MAPK, PI3K/AKT, and NF-κB pro-survival pathways was observed. These cellular changes were accompanied by apoptotic morphological features visualized by PlasDIC and brightfield microscopy, including membrane blebbing, karyorrhexis, and apoptotic body formation. Collectively, these findings demonstrate concurrent redox disturbance, mitochondrial dysfunction, and apoptosis following supraphysiological vitamin D exposure. NAC co-treatment produced partial attenuation of the ROS-positive population and improved mean viability following calcipotriol treatment, supporting a possible contribution of ROS to calcipotriol-associated cytotoxicity; however, the present experiments do not establish ROS as a necessary mediator of apoptosis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816483","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":"HIF1A-Associated Ferroptosis-Related Gene Signatures Reveal Candidate Circulating Biomarkers in Diabetic Nephropathy","authors":"Yufeng Li,&nbsp;Jiao Bao,&nbsp;Rong Sun,&nbsp;Wenjie Mei,&nbsp;Yonghong Liu,&nbsp;Yan Bai,&nbsp;Chengxiang Hu,&nbsp;Hongying Jiang","doi":"10.1096/fba.2026-00173","DOIUrl":"10.1096/fba.2026-00173","url":null,"abstract":"<p>Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Hypoxia-inducible factor 1-alpha (HIF1A) and ferroptosis contribute to the progression of DN, but the circulating biomarkers associated with these pathways are still unknown. In this study, the whole-blood transcriptomic datasets in the Gene Expression Omnibus were combined with ferroptosis-related genes from the FerrDb database and published literature. The differentially expressed genes of HIF1A and of DN were intersected, and then the feature selection with Boruta and SVM-RFE was performed, followed by external validation, immune infiltration analysis, prediction of regulatory network, drug-target prediction, and RT-qPCR validation. We identified 773 HIF1A-related genes, 1445 DN-related genes, and 22 overlapping candidate genes. Using machine-learning analysis, nine core genes were identified, including SLC7A5 and SLC2A14, which consistently upregulated in both training and validation datasets and corroborated by RT-qPCR. Both genes were positively associated with activated natural killer cells and negatively associated with monocytes in estimated circulating immune-cell composition analysis. Regulatory-network and DrugBank analyses generated hypotheses regarding upstream miRNAs and potential compound interaction. These findings identify SLC7A5 and SLC2A14 as candidate circulating biomarkers related to HIF1A expression and ferroptosis-related gene signatures in DN. Further large-cohort and functional studies are required to confirm their diagnostic and mechanistic relevance.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817816","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":"Integrated Molecular and Phenotypic Profiling of Circulating Tumor Cells in Gastric Cancer: A Translational Perspective","authors":"Mohammad Reza Eskandarion,&nbsp;Sharareh Eskandarieh,&nbsp;Abbas Shakoori Farahani,&nbsp;Farideh Ghanbari Mardasi,&nbsp;Habibollah Mahmoodzadeh,&nbsp;Kamran Roudini,&nbsp;Farhad Shahi,&nbsp;Mohammad Ali Oghabian,&nbsp;Mohammad Taher,&nbsp;Reza Shirkoohi","doi":"10.1096/fba.2025-00314","DOIUrl":"https://doi.org/10.1096/fba.2025-00314","url":null,"abstract":"&lt;p&gt;Gastric cancer often presents at advanced stages, limiting treatment outcomes. Circulating tumor cells (CTCs), particularly those undergoing epithelial–mesenchymal transition (EMT), have emerged as promising biomarkers for real-time disease monitoring. Using magnetic-activated cell sorting (MACS), we enriched both epithelial (EpCAM&lt;sup&gt;+&lt;/sup&gt;) and mesenchymal (CD90&lt;sup&gt;+&lt;/sup&gt;) CTCs and evaluated the expression of the tumor-suppressive microRNA miR-29b in CTCs of gastric cancer patients. This study aimed to explore the clinical relevance of perioperative CTC phenotypes and miR-29b as potential diagnostic and prognostic markers. We conducted a multi-phase study integrating systematic review, bioinformatics, and experimental analyses to investigate CTC phenotypes and ECM-associated gene expression in GC. Peripheral blood samples were collected from 30 treatment-naïve gastric cancer patients at two time points: before initiation of therapy and 1 month after curative-intent gastrectomy. Circulating tumor cells (CTCs) were isolated using CD45-negative magnetic-activated cell sorting (MACS). Immunofluorescence staining was performed to phenotype CTCs based on EpCAM (epithelial) and CD90 (mesenchymal) expression. Total RNA was extracted from tumor tissues and isolated CTCs to evaluate ECM-related genes and miR-29b expression using quantitative real-time PCR. Bioinformatics-guided gene selection and statistical analysis were used to assess diagnostic and prognostic relevance. CTCs were detected in 83.3% (25/30) of gastric cancer patients prior to treatment. Mesenchymal CTCs (CD90&lt;sup&gt;+&lt;/sup&gt;) were markedly more frequent than epithelial CTCs (EpCAM&lt;sup&gt;+&lt;/sup&gt;), with mean baseline counts of 14.07 versus 0.5 cells per 10 mL of blood, respectively. Following gastrectomy and chemotherapy, mesenchymal CTCs significantly declined (mean: 1.18; &lt;i&gt;p&lt;/i&gt; = 0.0064), while epithelial CTCs were nearly undetectable (&lt;i&gt;p&lt;/i&gt; = 0.0246). Based on perioperative CTC dynamics, patients were stratified into three risk groups: high-risk (16%), intermediate-risk (68%), and low-risk (16%). All observed deaths occurred in the high-risk group during 14 months of follow-up, with Kaplan–Meier analysis showing significantly lower survival in this group (&lt;i&gt;p&lt;/i&gt; = 0.0107). Expression analysis revealed significant downregulation of miR-29b in tumor tissues (fold change = 0.5163; &lt;i&gt;p&lt;/i&gt; = 0.0136) and in CTCs (fold change = 0.2049; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) compared to healthy controls. Although miR-29b levels were broadly downregulated in gastric cancer patients, no significant differences were observed among clinicopathological subgroups within the patient cohort. ROC analysis showed strong diagnostic performance of miR-29b in tissue (AUC = 0.883, 95% CI: 0.798–0.969), with 96.7% sensitivity and 70% specificity. CD90 serves as a sensitive mesenchymal marker for detecting CTCs that lack epithelial features, enabling more comprehensive identification of aggressive CTC phenotypes in","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783974","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":"Exploring the BICC1 Interactome in HEK293T Cells: Insights Into RNA-Mediated Protein Networks and Biomolecular Condensates","authors":"Heloísa Monteiro do Amaral-Prado,&nbsp;Gabriela Alves Moreira,&nbsp;Cristiane Santos,&nbsp;Fernando Henrique Bosso,&nbsp;Felipe Eduardo Ciamponi,&nbsp;Guilherme Oliveira Barbosa,&nbsp;Mario Henrique Bengtson,&nbsp;Katlin Brauer Massirer","doi":"10.1096/fba.2026-00035","DOIUrl":"10.1096/fba.2026-00035","url":null,"abstract":"<p>Bicaudal C Homolog 1 (BICC1) is a conserved RNA-binding protein that, in mammals, has been primarily associated with polycystic kidney disease and renal organogenesis. However, its role in other disease contexts, including cancer, remains poorly understood. In this study, we characterized the BICC1 interactome, with emphasis on its dependence on RNA and the sterile alpha motif (SAM) domain, to identify novel biological processes associated with BICC1 function. Protein complexes were purified from HEK293T cells by co-immunoprecipitation and analyzed by mass spectrometry. Notably, co-immunoprecipitations performed in the presence of RNA yielded a larger number of interacting proteins, with 31 of 71 proteins (~43%) uniquely identified under RNA-preserved conditions, highlighting the critical role of RNA in mediating BICC1 protein–protein interactions. Enriched proteins were predominantly associated with mRNA splicing, the PRMT5 methylosome complex, and membraneless organelles, such as biomolecular condensates. Consistent with these findings, immunofluorescence assays performed on stressed cells revealed the co-localization of BICC1 with stress granule markers. Moreover, BICC1 interactions with PRMT5, STK38, PARP1, and IGF2BP1 were confirmed by immunoblotting.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697282","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}