BioFactors最新文献

{"title":"VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiation.","authors":"Yuhan He, Ziyi Wang, Yao Weng, Heriati Sitosari, Yilin Zheng, Yaxin Qu, Mika Ikegame, Hirohiko Okamura","doi":"10.1002/biof.70104","DOIUrl":"10.1002/biof.70104","url":null,"abstract":"<p><p>Vestigial-like family member 3 (VGLL3), a transcriptional cofactor of the TEA domain family, has been previously identified as a regulator of osteoblast differentiation. Building upon our previous findings, we investigated VGLL3 function in MC3T3-E1 osteoblasts using an integrated approach combining transcriptomic analysis and functional assays to identify its downstream effectors and explore associated autophagy mechanisms. RNA-seq analysis of Vgll3-knockdown (shVgll3) cells identified death-associated protein kinase 2 (DAPK2), a regulator of autophagy, as a downstream effector. Autophagic activity was examined using transmission electron microscopy and western blot analysis of LC3-II and p62 proteins. The effects of Dapk2 knockdown (shDapk2) on osteoblast differentiation were evaluated using qPCR, western blotting, alkaline phosphatase staining, and Alizarin Red staining. Rapamycin treatment was used to determine whether pharmacologic activation of autophagy could restore osteoblast function. Vgll3 knockdown significantly suppressed autophagic flux, as evidenced by fewer autophagic vacuoles, decreased LC3-II accumulation, and increased p62 expression. A comparable reduction in autophagic activity was observed in shDapk2 cells and was accompanied by impaired osteoblast differentiation. Rapamycin treatment partially restored autophagy and osteogenic differentiation in Vgll3-deficient cells. Finally, overexpression of DAPK2 partially rescued autophagic activity and osteogenic differentiation in shVgll3 cells, supporting its role as a key downstream functional effector. FOXM1 was further implicated as a potential transcriptional regulator contributing to DAPK2 expression. Collectively, our findings suggest that VGLL3 may influence osteogenic differentiation in osteoblasts, potentially involving DAPK2-associated autophagy.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":"e70104"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761206","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":"Angiotensin II Promotes the Phenotypic Transition of c-Kit⁺ Cardiac Interstitial Cells to Myofibroblasts Through Collagen Receptor Discoidin Domain Receptor 2.","authors":"Indraja Devidasan, Sruthi Radhakrishnan, Sarayu Gopal, Geethu S Nair, Divya Mundackal Sivaraman, Vivek V Pillai, Neethu Mohan","doi":"10.1002/biof.70108","DOIUrl":"https://doi.org/10.1002/biof.70108","url":null,"abstract":"<p><p>Angiotensin II (Ang II), a potent profibrotic stimulus, exhibits pleiotropic effects on cardiac cells. The fate of c-Kit⁺ cells in an Ang II-elevated injured myocardium remains poorly defined. This study investigated, in vitro, the effect of Ang II on the phenotype of non-hematopoietic non-endothelial c-Kit⁺ cardiac interstitial cells (CICs), expressing OCT4. Our findings demonstrate that Ang II directly drives the phenotypic transition of c-Kit⁺ CICs into α-SMA-expressing myofibroblasts, accompanied by significant upregulation of prominent myofibroblast markers, SM22-α, collagen type IA, and its crosslinking enzyme, lysyl oxidase. Through targeted silencing experiments, we confirmed that Ang II-mediated phenotypic transition occurs via activation of the ERK1/2 MAPK pathway, triggered by collagen receptor Discoidin domain receptor 2 (DDR2), and involves the transcription factor, serum response factor (SRF). These results indicate that c-Kit⁺ CICs are susceptible to myofibroblast transition in the infarcted myocardium, and may serve as an additional source of myofibroblasts contributing to repair and remodeling alongside resident fibroblasts. Additionally, we observed that overexpression of c-Kit attenuated Ang II-induced α-SMA upregulation by downregulating DDR2-ERK1/2-SRF signaling in c-Kit⁺ CICs, highlighting the pivotal role of c-Kit expression levels in regulating cell fate. Furthermore, overexpression of c-Kit in Ang II-treated cardiac fibroblasts significantly reduced the expression of myofibroblast proteins, α-SMA, SM22-α, periostin, collagen type IA, collagen receptor DDR2, and lysyl oxidase, and resembled c-Kit⁺ CICs in morphology. Collectively, these results suggest that c-Kit expression in myofibroblasts may potentially mitigate the adverse effects of cardiac fibrosis and promote favorable remodeling in the long term.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":"e70108"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue Virus Capsid Protein Interaction With Nucleic Acids.","authors":"Nelly M Silva, Ana S Martins, Nina E Karguth, Maria J Sarmento, Francisco J Enguita, Roland G Huber, Ivo C Martins, Nuno C Santos","doi":"10.1002/biof.70105","DOIUrl":"10.1002/biof.70105","url":null,"abstract":"<p><p>Dengue virus (DENV) transmission has greatly increased in the last decade, partly due to the geographical expansion of Aedes spp. mosquitoes. These arthropods are now found even in temperate climates, including Europe, where outbreaks have occurred. A better understanding of the life cycle is essential, as it may enable the development of specific treatments or therapies, which are currently lacking. Recent breakthroughs concerning the viral capsid (C) protein structure and function are encouraging. It is now clear that the C protein binds both to host lipid droplets and to the viral genome-interactions crucial for viral encapsidation and replication. Here, we investigate how DENV C associates with the viral genome. Using DENV C and single-stranded DNA sequences analogous to relevant genomic regions, we biophysically characterize their interaction. A decrease in fluorescence intensity and lifetime, as well as changes in the protein secondary structure, were observed upon interacting with single-stranded DNA. These results are consistent with molecular condensation, supporting a possible liquid-liquid phase separation contributing to DENV C-nucleic acid complex formation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":"e70105"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761167","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":"Effects of a Commercial Standardized Green Rooibos (Aspalathus linearis) Extract on Caenorhabditis elegans and Zebrafish Anxiety-Like Behavior.","authors":"David G Valcarce, Sonia Guilera, Ferran Balaguer, Nuria Gonzalez, Miren Maicas, Patricia Martorell, Juan Manuel Martínez Vázquez, Vanesa Robles, Antonio M Inarejos García","doi":"10.1002/biof.70107","DOIUrl":"https://doi.org/10.1002/biof.70107","url":null,"abstract":"<p><p>Anxiety-related disorders are among the most prevalent mental health conditions worldwide, driving interest in novel, plant-based interventions. This study aimed to evaluate the antioxidant activity and capacity to alleviate anxiety-like behavior of a commercially standardized green rooibos (Aspalathus linearis) powdered extract (GRE) in vivo. The GRE was chemically characterized using liquid and gas chromatography. Antioxidant capacity (survival and ROS levels upon oxidative stress) and anxiety-like behavior reduction (octanol avoidance test) were evaluated in the Caenorhabditis elegans model, and additionally in adult zebrafish (Danio rerio) by a Novel Tank Test after 4 months of GRE ingestion. Analytical results of GRE confirmed the presence of dihydrochalcones (aspalathin, nothofagin) and flavones (orientin, isoorientin, isovitexin) as the major phenolic constituents. In C. elegans, GRE supplementation improved survival under oxidative stress conditions and significantly reduced intracellular ROS levels in a dose-dependent manner. Additionally, GRE exposure mitigated anxiety-like behavior in nematodes subjected to serotonin-deficiency conditions induced by starvation. GRE-fed fish exhibited a significant increase in time spent in the upper zone of the tank, reduced latency to reach this zone, and fewer individuals displaying bottom-dwelling behavior, while locomotor parameters (speed and distance traveled) remained unaffected, indicating reduced anxiety-like behavior levels. Data support the potential of GRE to reduce anxiety-related behavior in both invertebrate and vertebrate models, possibly mediated by its antioxidant properties and polyphenolic profile. These findings underscore the potential of A. linearis as a functional botanical candidate for future dietary interventions for anxiety support.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":"e70107"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Alternating Current Electrical Stimulation Parameters to Enhance Osteoblasts Differentiation","authors":"Jesús Bocio-Núñez,&nbsp;Mª. José Montoya-García,&nbsp;Mª. Ángeles Vázquez-Gámez,&nbsp;Daniel Martín,&nbsp;Pedro Chacón,&nbsp;Miguel Ángel Rico,&nbsp;Miguel Ángel Colmenero,&nbsp;Alberto Yufera,&nbsp;Mercè Giner","doi":"10.1002/biof.70097","DOIUrl":"10.1002/biof.70097","url":null,"abstract":"<p>Electrical stimulation (ES) has emerged as a promising technique in the field of bioengineering and biomedicine, particularly in bone regeneration and cell differentiation. ES using alternating current (AC) is based on the periodic reversal of current direction, which generates oscillating electric fields. The application of an electric field has effects on cell growth and differentiation, as well as on morphology and migration. This study aimed to explore the effect of applying AC electrostimulation within the proliferation, differentiation, and morphology process of osteoblastic cells. The electrical stimulation signals were daily applied for 3 h during 14 days. Different frequencies were tested (1 Hz, 10 Hz, 100 Hz, and 1 kHz), with amplitudes of 125, 250, 500, 750, 1000, and 1500 mV/mm. Cell viability was estimated using the AlamarBlue, and MC3T3-E1 differentiation levels were evaluated through alkaline phosphatase (ALP) activity. <i>RUNX2</i>, <i>OSX</i>, <i>ALP</i>, <i>OPG</i>, and <i>RANKL</i> gene expression was assessed by RT-PCR. Morphological analysis was performed through cell transfection followed by immunofluorescence. Statistical analysis was conducted by SPSS.23 and graphs generated through Graph-pad. Viability and ALP activity were optimal at 10 Hz. Once the frequency was defined, <i>RUNX2</i>, <i>OSX</i>, <i>ALP</i>, <i>OPG</i>, and <i>RANKL</i> gene expression revealed an increase in the differentiation and osteogenic activity levels at 10 Hz and 500–750 mV/mm. As well as, morphological studies showed an increase in the area, pseudopodia length, and numbers at 500 mV 10 Hz conditions. The optimal ES condition to differentiate MC3T3-E1 cells is 10 Hz 500–750 mV/mm. Electrostimulation has emerged as a promising technique in the field of bioengineering and biomedicine, particularly in bone regeneration and cell early maturation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670106","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":"Eupatilin Ameliorates Sepsis-Induced Myocardial Injury by Targeting the KAT5-H3K27la Epigenetic Axis","authors":"Qianqian Du,&nbsp;Shuwan Hou,&nbsp;Minfu Liu,&nbsp;Jiaqin Wu,&nbsp;Huiming Yu,&nbsp;Fan Feng,&nbsp;Huaping Liang,&nbsp;Chunli Wang,&nbsp;Kang Xu,&nbsp;Qingjia Chi","doi":"10.1002/biof.70094","DOIUrl":"10.1002/biof.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis induced myocardial injury (SIMI) remains a life threatening complication with mortality rates exceeding 40% to 50%, yet effective therapies are lacking. This study investigates the cardioprotective effects of eupatilin (EUP), a bioactive flavonoid derived from Artemisia argyi, and reveals a previously unrecognized mechanism involving selective modulation of KAT5 mediated histone H3K27 lactylation (H3K27la). Using an LPS induced murine model and TNF-α stimulated human AC16 cardiomyocytes, we evaluated cardiac function, inflammatory responses, and apoptotic pathways through dose response analyses. Multi omics approaches including RNA seq, metabolomics, ChIP seq, and molecular docking were integrated to dissect the pharmacodynamic profile of EUP. EUP conferred concentration dependent cardioprotection with optimal effects at 25 μM. Compared with conventional glucocorticoid therapy, EUP showed enhanced target selectivity, markedly reducing pro inflammatory cytokines such as TNF-α, IL-1β, and IL-6 while improving cardiac function parameters including ejection fraction and fractional shortening. Mechanistically, EUP bound KAT5 with high affinity, suppressed its lactylation activity, and reduced H3K27la enrichment at the promoters of inflammatory genes. Metabolic flux analysis further indicated that EUP inhibited glycolytic lactate production and restored oxidative phosphorylation. Together, these findings identify EUP as a natural modulator of the KAT5-H3K27la axis, addressing both metabolic dysregulation and epigenetic reprogramming in SIMI. With a favorable pharmacokinetic profile and superior target specificity relative to standard immunosuppressive regimens, EUP holds promise for clinical translation in sepsis associated cardiac dysfunction.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is There an Ace Up One's Sleeve in the Preanalytical Phase of the Circulating Tumor DNA Analysis?","authors":"Juscelino Carvalho de Azevedo Junior,&nbsp;Douglas Rafael da Cruz Carneiro,&nbsp;Fernanda Jardim da Silva,&nbsp;Ana Beatriz Lima Belicha,&nbsp;Anna Carolina Lima Rodrigues,&nbsp;Williams Fernandes Barra,&nbsp;Alessandro Leal,&nbsp;Danielle Queiroz Calcagno","doi":"10.1002/biof.70095","DOIUrl":"10.1002/biof.70095","url":null,"abstract":"<p>Circulating tumor DNA (ctDNA) analysis has emerged as a pivotal minimally invasive tool for early detection, monitoring, and treatment stratification in cancer patients. However, the accuracy and reliability of ctDNA assays are profoundly influenced by preanalytical variables. This review discusses the impact of biological features (circadian rhythm, age, and sex), lifestyle factors (diet, smoking, and physical activity), as well as technical aspects such as hemolysis, leukocyte lysis, and delayed plasma separation on ctDNA integrity and concentration. Fluctuations in ctDNA levels driven by these factors highlight the need for clear guidelines regarding precollection timing, dietary restrictions, and sample processing. Furthermore, the adoption of harmonized protocols is essential to reduce variability and improve reproducibility across clinical and research settings.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571991","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":"L-Dopa Decarboxylase Mediates Apoptosis Through Regulation of PI3K/AKT Pathway in Response to DENV Infection","authors":"Evangelos Korakidis,&nbsp;Eirini Kyriakopoulou,&nbsp;Katerina I. Kalliampakou,&nbsp;George Mpekoulis,&nbsp;Iris Kolida,&nbsp;Eirini P. Kollia,&nbsp;Elli-Anna Stylianaki,&nbsp;Vassiliki Vassilaki,&nbsp;Konstantina Koukoutsi,&nbsp;Despoina P. Kiouri,&nbsp;Georgios C. Batsis,&nbsp;Sofia Marka,&nbsp;Dionysis Kefallinos,&nbsp;Despoina Smirlis,&nbsp;Evangelia Xingi,&nbsp;Marianna H. Antonelou,&nbsp;Diamantis Sideris,&nbsp;Christos T. Chasapis,&nbsp;Konstantinos Kambas,&nbsp;Dido Vassilacopoulou,&nbsp;Niki Vassilaki","doi":"10.1002/biof.70093","DOIUrl":"10.1002/biof.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>L-dopa decarboxylase (DDC) is the biosynthetic enzyme of dopamine and serotonin. Although DDC has been originally studied for its role in neurotransmission, it has also been detected in peripheral organs, where it is implicated in cellular homeostasis. DDC has been identified by our research team as a negative regulator of dengue virus (DENV) replication in liver cells. The latter has been attributed, at least in part, to the physical interaction of DDC protein with phosphatidylinositol 3-kinase (PI3K), and its biosynthetic function. PI3K/AKT signaling and cell survival are manipulated by DENV to favor its replication. Based on the above, we investigated whether DDC exerts its antiviral activity against DENV propagation through modulation of DENV-induced cell death and especially apoptosis. Specifically, <i>DDC</i> silencing in Huh7.5 cells (shDDC) significantly reduced virus-induced cytopathic effect compared to the control cells (shControl). This finding was accompanied by suppression of both early and later stages of apoptosis in the silenced cells, as shown by Annexin V/PI staining and TUNEL assay, respectively. Accordingly, upon infection, shDDC cells showed suppressed activation of key caspases, BCL-2 family members and TRAIL-receptor genes that modulate the apoptotic cascade, compared to the control cells. Moreover, mitochondrial analysis in DENV-infected cells revealed that, upon <i>DDC</i> silencing, a less pronounced disruption of mitochondrial membrane potential and network integrity, higher respiratory capacity, lower ROS production, and reduced cytochrome c release were observed. As the PI3K/AKT pathway is known to be affected by both DENV and DDC, next we assessed whether DDC is involved in the virus-induced apoptosis through this axis. For this, we quantified the reduction of p-AKT and p-mTOR levels caused by DENV infection in the two cell lines, which was found greater in the shControl cells. Finally, chemical inhibition of AKT phosphorylation abolished the differences in cell viability and apoptosis between the two cell lines. In total, our findings highlight the suppressive role of DDC against DENV replication by modulating the PI3K/AKT-dependent apoptotic signaling.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETV1 Promotes Glioma Progression via miR-3175/STEAP2 Axis","authors":"Zichen Liu,&nbsp;Wenshuai Deng,&nbsp;Zuoxiang Dong,&nbsp;Peng Sun","doi":"10.1002/biof.70090","DOIUrl":"10.1002/biof.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma is lethal brain tumor with dismal prognosis. ETV1, an ETS family transcription factor, has been implicated in multiple malignancies, yet its precise role and regulatory mechanisms in glioma progression remain incompletely defined. This study investigated the role of ETV1 in maintaining the malignant phenotype of high-grade gliomas through a novel regulatory axis involving microRNA-3175 (miR-3175) and STEAP2. ETV1 expression was analyzed in TCGA glioma datasets (<i>n</i> = 692) and 85 patient tissue specimens using bioinformatics, quantitative RT-PCR, Western blotting, and immunohistochemistry. ETV1 function was assessed through gain-of-function and loss-of-function studies in glioma cell lines (U251, A172) and validated in nude mouse xenografts with bioluminescence imaging. The ETV1-miR-3175-STEAP2 regulatory axis was characterized using chromatin immunoprecipitation, luciferase reporter assays, biotin-streptavidin pulldown, RNA immunoprecipitation, and rescue experiments. ETV1 was significantly upregulated in gliomas, with expression correlating to tumor grade and reduced overall patient survival. ETV1 overexpression promoted glioma cell proliferation, migration, and invasion in vitro and enhanced tumor growth while reducing survival in vivo, with elevated bioluminescence radiance indicating enhanced tumorigenicity, whereas ETV1 knockdown produced opposite effects and diminished bioluminescent signals. ETV1 transcriptionally activated miR-3175 through direct binding to its promoter. miR-3175 directly targeted and suppressed STEAP2 expression via conserved 3′UTR binding sites. STEAP2 functioned as a tumor suppressor; overexpression inhibited malignant phenotypes. Rescue experiments confirmed miR-3175 and STEAP2 mediate ETV1-driven glioma progression through a functional ETV1/miR-3175/STEAP2 regulatory axis. This study revealed a novel ETV1/miR-3175/STEAP2 regulatory axis driving glioma tumorigenesis and identified potential therapeutic targets for intervention.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANXA5: A Multi-Omics-Derived, UPR-Associated Dual-Function Biomarker for Prognosis and Immunotherapy Response Prediction in Glioma","authors":"Jiachong Wang,&nbsp;Haijun Guo,&nbsp;Wei Zheng,&nbsp;Maximo Lin,&nbsp;Chunyuan Zhang,&nbsp;Biying Zeng,&nbsp;Duorong Wu,&nbsp;Zigui Chen,&nbsp;Changfeng Miao,&nbsp;Chunhai Tang,&nbsp;Qisheng Luo","doi":"10.1002/biof.70092","DOIUrl":"10.1002/biof.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioma, a highly aggressive brain cancer, thrives in an immunosuppressive tumor microenvironment (TME). The Unfolded Protein Response (UPR) is a key adaptive stress pathway implicated in therapy resistance. To discover clinically actionable biomarkers, we employed an integrated multi-omics strategy, combining single-cell and bulk transcriptomic data from multiple glioma cohorts. Using hdWGCNA network analysis, we identified a UPR-associated gene module that defined two molecular subtypes with stark survival differences. Through a rigorous machine learning pipeline (Random Survival Forest, LASSO, and CoxBoost), ANXA5 emerged as the central prognostic gene. High ANXA5 expression consistently predicted poorer overall survival across eight independent datasets, validating its robust prognostic value. Functionally, ANXA5 was linked to extracellular matrix remodeling and immune modulation. Multi-omics profiling revealed that ANXA5-high gliomas exhibit a T-cell-inflamed yet immunosuppressive TME, characterized by elevated immune checkpoint expression. Crucially, ANXA5 demonstrated strong predictive power for response to immune checkpoint blockade (ICB), showing significant correlation with nine established immunotherapy response signatures and accurately discriminating responders from non-responders in six independent ICB-treated clinical cohorts (AUC: 0.65–0.78). Genomic analysis associated ANXA5 expression with distinct mutation patterns (EGFR/PTEN vs. IDH1/TP53). In vitro knockdown of ANXA5 confirmed its oncogenic role, as it suppressed glioma cell proliferation and invasion. Our study establishes ANXA5 as a prime example of a translatable biomarker discovered through multi-omics integration. It functions dually as a prognostic indicator and a predictive biomarker for immunotherapy, offering a tangible framework for patient stratification and personalized therapeutic strategies in glioma, thereby bridging a critical gap toward clinical translation.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}