Biochemistry and Biophysics Reports最新文献

{"title":"NOHA as a key biomarker to link NOS2 activity to immune checkpoint and cytokine signaling in ER-negative breast cancer","authors":"Olivia Chase,&nbsp;Emmeline Graham,&nbsp;Mack Buczek,&nbsp;William Speltz,&nbsp;Megan Steele,&nbsp;Connor LaBonte,&nbsp;Srinidi Mohan","doi":"10.1016/j.bbrep.2026.102468","DOIUrl":"10.1016/j.bbrep.2026.102468","url":null,"abstract":"<div><h3>Background</h3><div>Estrogen receptor–negative (ER−) breast cancer remains clinically challenging due to its aggressive behavior, lack of targeted therapies, and limited biomarker tools for diagnosis and disease monitoring. While immune checkpoint markers (such as PD-L1) and inflammatory cytokines (viz., IL8) offer insight into tumor immune dynamics, their clinical application is hampered by tissue-dependence and/or biological variability. We have previously delineated N^w-hydroxy <span>l</span>-Arginine, (NOHA) as a simple, yet sensitive biomarker in distinguishing breast cancer based on estrogen-hormone-receptor status (USPTO 10,073,099). This study investigates whether NOHA functions as key biomarker linking immune checkpoint activation and inflammatory cytokine signaling in ER− breast cancer.</div></div><div><h3>Methods</h3><div>Three-dimensional (3D) spheroid cultures were generated from ER− and ER + breast cancer cell lines of African American (AA) and Caucasian (CA) origin, as well as healthy control cells. 3D spheroids were maintained for 7 weeks, with weekly measurements of their medium NOHA as well as lysates for cellular NOHA, NOS2 activity, total nitrites, PD-L1, and IL-8. Quantification was performed using validated ELISA and fluorometric assays. Statistical comparisons were performed using ANOVA with post-hoc testing.</div></div><div><h3>Results</h3><div>ER− spheroids exhibited a progressive ≥1-fold increase in cellular NOS2, total nitrites, PD-L1, and IL-8, accompanied by a ≥1-fold decrease in both cellular and medium NOHA over 7 weeks (p &lt; 0.01). No significant changes were observed in ER + or control spheroids. The ratio means of cellular PD-L1/medium NOHA and cellular IL-8/medium NOHA increased significantly in ER− groups, with AA-derived ER– 3D spheroids demonstrating ≥43.8 % and ≥48.4 % higher mean ratios, respectively, compared to ER– CA-derived counterparts (p &lt; 0.01). A corresponding analysis comparing ratio means of cellular PD-L1/cellular NOHA and cellular IL-8/cellular NOHA showed a similar pattern, with ≥52.4 % and ≥55.9 % higher mean ratios in ER− groups, with AA-derived ER– 3D spheroids, than in ER– CA group (p &lt; 0.01).</div></div><div><h3>Discussion</h3><div>These findings identify NOHA as a potential non-invasive biomarker that reflects dynamic immuno-inflammatory changes in ER− breast cancer. The inverse relationship between NOHA and both PD-L1 and IL-8 suggests an inflammatory loop driven by NOS2 activity. The pronounced effects in AA-derived ER− spheroids align with known disparities in tumor aggressiveness and suggest future NOHA clinical utility potential in racially diverse populations. Further in vivo validation is warranted to support and confirm such clinical translation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102468"},"PeriodicalIF":2.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-sequencing based gene variants observed in patients with hyperlipidemia and premature coronary heart disease: A preliminary study","authors":"Wilanee Dechkhajorn ,&nbsp;Kriengchai Prasongsukarn ,&nbsp;Surachet Benjathummarak ,&nbsp;Supachai Topanurak ,&nbsp;Yaowapa Maneerat","doi":"10.1016/j.bbrep.2026.102466","DOIUrl":"10.1016/j.bbrep.2026.102466","url":null,"abstract":"<div><div>Familial hypercholesterolemia (FH) is a genetic disorder characterized by markedly elevated low-density lipoprotein (LDL) cholesterol levels, which primarily progresses to premature or familial coronary heart disease (FH-CHD).</div><div>This cross-sectional study included healthy controls (N) and patients with hyperlipidemia (H), FH, CHD, and FH-CHD. We attempted to explore gene variants shared in H, FH and FH-CHD using next-generation sequencing tool. The RNA-seq transcriptome profiling from the whole peripheral blood (n = 3/group) were analyzed. The results revealed 15 intersected gene variants between the H/FH and FH-CHD groups. Aligning and mapping on the coding regions showed significant high-impact variants in 6 of the 15 genes including <em>MAFG</em>, <em>AKAP1</em>, <em>TLR5</em>, <em>CHUK, EMC10,</em> and <em>PLRG1.</em> The significant high-impact variations included frameshift variants in <em>CHUK</em> and <em>PLRG,</em> stop-gain variation in <em>TLR5</em> at the last intron, stop-lost variation in <em>EMC10,</em> and splice-acceptor and donor variants in <em>MAFG</em> and <em>AKAP1</em>, respectively. Pathogenicity scoring (ACMG Criteria) interpreted that these variation effects are predicted to lose the gene functions. Based on reference databases without any validation, these gene variations are probably linked to atherogenesis and CHD development.</div><div>Conclusively, our exploratory observed that <em>MAFG</em>, <em>AKAP1</em>, <em>TLR5</em>, <em>CHUK, EMC10,</em> and <em>PLRG1</em> variants had higher impacts and might be related to premature CHD development. Further classification and functional validation of these genetic variations should be considered for the feasibility of using these gene variants as contributory predictors of the FH-CHD risk in hyperlipidemia patients.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102466"},"PeriodicalIF":2.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chidamide and Anlotinib act synergistically in Jurkat cells by inhibiting the Hippo signaling pathway","authors":"Tao Ma ,&nbsp;Yuan Yu ,&nbsp;Shuting Yang ,&nbsp;Qiong Xiao ,&nbsp;Xiuqin Zuo ,&nbsp;Gang Wei ,&nbsp;Yan Chen","doi":"10.1016/j.bbrep.2026.102469","DOIUrl":"10.1016/j.bbrep.2026.102469","url":null,"abstract":"<div><h3>Background</h3><div>T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive hematologic malignancy characterized by drug resistance, relapse and poor prognosis. Chidamide, a histone deacetylase inhibitor, has shown epigenetic therapeutic potential in T-ALL, but its efficacy is limited and acquired drug resistance exists. To overcome these limitations, we systematically evaluated the synergistic Combination effects of three drug candidates, OTX-015 (BET inhibitor), Metformin (metabolic regulator), and Anlotinib (multitargeted tyrosine kinase inhibitor), with Chidamide.</div></div><div><h3>Methods</h3><div>We chose Jurkat cells, a cell line for T-ALL, for our experiments. With the CCK-8 trial, we chose the most efficacious Combination of Anlotinib and Chidamide, for the follow-up trial. The antitumor activity of Chidamide and Anlotinib alone or in Combination on Jurkat cells was detected by cell proliferation, apoptosis and cell cycle assay. Transcriptome sequencing and Western blotting were used to identify the key signaling pathways.</div></div><div><h3>Results</h3><div>Jurkat cells treated with Anlotinib showed significant inhibition of cell viability, G2/M arrest and apoptosis. Combination therapy with Chidamide synergistically potentiates these effects. Mechanistically, the Combination treatment inhibited the components of the Hippo pathway (<em>CCN2</em> and <em>YAP</em>), suppressed the PI3K-Akt signaling pathway, and remodeled the expression of extracellular matrix (ECM) -related genes. Transcriptomic analysis further highlighted the enrichment of ECM organization and PI3K-Akt pathway.</div></div><div><h3>Conclusions</h3><div>Chidamide and Anlotinib synergistically inhibit Hippo signaling pathway, which reveals a novel “dual epigenetic kinase targeting” strategy for the treatment of T-ALL. Future studies should validate these findings in vivo and investigate the impact of the metabolic microenvironment on therapeutic efficacy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102469"},"PeriodicalIF":2.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation","authors":"Panjiao Pang,&nbsp;Mingyang Yu,&nbsp;Huixin Ma,&nbsp;Longkai Wei,&nbsp;Jiali Huang,&nbsp;Lingxin Zhao,&nbsp;Ying-hua Zhang","doi":"10.1016/j.bbrep.2026.102464","DOIUrl":"10.1016/j.bbrep.2026.102464","url":null,"abstract":"<div><div>The localization and translation of mRNAs play crucial roles in maintaining cellular phenotype and function, with RNA-binding protein (RBP) contributing significantly to these processes. TAR DNA-binding protein of 43 kDa (TDP-43) is an RNA/DNA-binding protein that is primarily localized in the nucleus, where it performs essential functions in pre-mRNA splicing, mRNA transport, and the stabilization and localized translation of mRNA. Its mis-localization from the cytoplasm, as well as mutations, protein misfolding, and posttranslational modifications, is closely linked to a reduction in its RNA-binding ability. This functional impairment is implicated in the initiation and progression of neurodegenerative diseases and cancer. In this review, we begin with a retrospective analysis of the molecular mechanism by which distinct domains of TDP-43 contribute to the initiation and progression of disease, particularly because its overexpression in tumors significantly influences disease progression. We subsequently elucidate the classical mechanisms of mRNA localization and translation, while clarifying the role of TDP-43 in these processes. Finally, we summarize the mechanisms by which TDP-43 facilitates the formation of ribonucleoprotein particles and this protein's involvement in mRNA localization and translation, as well as its associated molecular pathways. In conclusion, this review highlights the critical roles of TDP-43 and subsequent therapeutic strategies for treatment of neurodegenerative diseases and tumors.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102464"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple and rapid method for generating antibodies against bovine alphaherpesvirus 1 viral proteins through immunization with virus-infected murine cells","authors":"Jiayu Lin ,&nbsp;Xiaozhen Ma ,&nbsp;Naifan Zhang ,&nbsp;Yue Pang ,&nbsp;Filomena Fiorito ,&nbsp;Xiuyan Ding ,&nbsp;Liqian Zhu","doi":"10.1016/j.bbrep.2026.102450","DOIUrl":"10.1016/j.bbrep.2026.102450","url":null,"abstract":"<div><div>Bovine alphaherpesvirus 1 (BoAHV-1) infects cattle and typically results in significant economic losses for the cattle industry worldwide. Currently, antibodies targeting only a limited number of viral proteins are commercially available. It has been reported that BoAHV-1 is capable of infecting numerous tumor cell lines. Based on the rationale of immune tolerance, we hypothesized that virus-infected murine cells could be directly used to immunize mice, thereby generating antibodies against viral proteins. In this study, we found that BoAHV-1 can infect murine cell lines including LA795 and MC38, as determined using both Western blot and immunofluorescence analyses. Immunizing mice with virus-infected cells, either through subcutaneous or intraperitoneal injection, stimulates the production of high levels of antibodies that specifically recognize the viral proteins synthesized in bovine kidney (MDBK) cells, as characterized by both Western blot and/or immunofluorescence. Furthermore, our findings suggest that intraperitoneal immunization could more effectively elicit antibodies against a wider array of viral proteins. As a homemade antibody generation method, this approach bypasses the complex and time-consuming steps of producing and purifying recombinant proteins as antigen, which are typically performed in conventional methods for antibody generation. Thus, we present a simple, rapid, and cost-effective method for generating virus-specific antibodies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102450"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The research progress of ferroptosis in acute lung injury","authors":"Yixuan Bai ,&nbsp;Yongming Ma ,&nbsp;Xingfang Li","doi":"10.1016/j.bbrep.2025.102434","DOIUrl":"10.1016/j.bbrep.2025.102434","url":null,"abstract":"<div><div>Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal mechanism in the pathogenesis of acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). Its core molecular machinery, including glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and the cystine/glutamate antiporter system Xc-, becomes dysregulated across various ALI subtypes, such as sepsis, ischemia-reperfusion, and COVID-19.This review delineates how ferroptosis contributes to ALI through iron overload, uncontrolled lipid peroxidation, and failure of antioxidant defenses, ultimately leading to pulmonary endothelial and epithelial cell death. We further summarize subtype-specific mechanisms and evaluate emerging therapeutic strategies, including ferroptosis inhibitors (e.g., liproxstatin-1), Nrf2 activators, and iron chelators, highlighting their potential for targeted intervention in ALI/ARDS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102434"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative metabolomic of cigar tobacco leaves: A preliminary investigation of potential discriminatory metabolites between Yunnan and Foreign","authors":"Gaokun Zhao,&nbsp;Guanghui Kong,&nbsp;Mengxia Li,&nbsp;Yuping Wu,&nbsp;Heng Yao,&nbsp;Wei Li,&nbsp;Huachan Xia,&nbsp;Guanghai Zhang","doi":"10.1016/j.bbrep.2026.102461","DOIUrl":"10.1016/j.bbrep.2026.102461","url":null,"abstract":"<div><div>A systematic understanding of the metabolic components in cigar tobacco leaves (CTLs) from different ecological regions remains limited. This study aimed to clarify the substance differences between CTLs from Yunnan and major foreign production areas and to identify potential discriminant metabolites. A total of 25 CTL samples were collected from four production areas in Yunnan and five different foreign countries. The metabolic profiles were comprehensively characterized using continuous flow analysis, ion chromatography, GC-MS, and UPLC-MS/MS. The results revealed that Yunnan CTLs were characterized by a lower sugar-nicotine ratio and significantly higher contents of starch, pectin, and lignin compared to foreign samples. Phenolic acids, alkaloids, flavonoids, amino acids and derivatives, terpenoids, and lipids were identified as the primary components across all CTLs. A total of 398 differential metabolites (248 volatile and 150 non-volatile) were identified, predominantly from the classes of amino acids and derivatives, alkaloids, terpenoids, and lipids. From these, 12 metabolites were selected as potential candidates for distinguishing CTL origin. KEGG enrichment and MetOrigin analyses indicated that the differential metabolites were mainly involved in the biosynthesis of alkaloids, amino acids, flavonoids, lipids, and terpenes, with these pathways being significantly influenced by microorganism and enzyme-mediated carbon and nitrogen coupling metabolism. This exploratory study provides a metabolic foundation for improving production techniques and for the analysis of style-defining substances in Yunnan CTLs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102461"},"PeriodicalIF":2.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis","authors":"Xinliao Sun ,&nbsp;Yuchang Gui ,&nbsp;Yuting Lu ,&nbsp;Kewen Wang ,&nbsp;Jingzhi Yao ,&nbsp;Zi Li ,&nbsp;Dandan Lu ,&nbsp;Qian Guo ,&nbsp;Ruixue Liu ,&nbsp;Jianwen Xu","doi":"10.1016/j.bbrep.2025.102439","DOIUrl":"10.1016/j.bbrep.2025.102439","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a serious condition typically caused by mechanical trauma, often resulting in significant motor, sensory, and autonomic dysfunction. It places a heavy burden on individuals, families, and society; however, effective treatment options are still limited because of the complex pathophysiology behind primary and secondary injury mechanisms. Neutrophil extracellular traps (NETs) created by neutrophils play a crucial role in exacerbating secondary injury following spinal cord injury by promoting inflammation and hindering neural repair. This study aims to clarify the molecular basis of neutrophil extracellular trap-related genes (NRGs) in SCI through an integrated bioinformatics approach. We utilized the GSE151371 dataset from the GEO database, which includes gene expression profiles from 38 SCI patients and 10 healthy controls, and we identified differentially expressed genes (DEGs) using the limma package in R. We identified 4878 DEGs, and we performed functional analysis of these genes using GO and KEGG. Immune cell infiltration analysis conducted with CIBERSORT showed significant differences in immune cell populations between the SCI group and the control group, with notable differences in the infiltration of Neutrophils, B cells memory and Macrophages M0. Weighted gene co-expression network analysis (WGCNA) identified a module highly associated with SCI, which resulted in the selection of 12 candidate genes. We built a predictive model using machine learning algorithms, identifying NLRP3, LRG1, and TLR8 as key genes with high diagnostic potential (AUC &gt;0.9). Subsequently, through multi-omics analysis, including gene set enrichment analysis (GESA), protein interaction analysis, and correlation analysis between key genes and immune cells, we explored the relationship between key NRGs and the pathological processes in SCI patients. Finally, these findings were validated through molecular biology experiments in a rat SCI model and clinical samples, confirming the clinical relevance of our findings regarding these biomarkers. In summary, this study provides a comprehensive analysis of NRGs in SCI, highlighting their diagnostic and therapeutic potential. Future research could focus on developing interventions targeting NETs formation, providing new opportunities to enhance treatment outcomes for SCI.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102439"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopic endometrial mesenchymal stem cell-derived exosomal miR-4466 promotes angiogenesis by targeting RUNX1 in adenomyosis","authors":"Jindan Wang ,&nbsp;Yongyan Ni ,&nbsp;Jiali Sun ,&nbsp;Yingying Qiu ,&nbsp;Xinjun Wei ,&nbsp;Bei Wang ,&nbsp;Meihua Huang ,&nbsp;Zhenli Li ,&nbsp;Tao Gui","doi":"10.1016/j.bbrep.2026.102457","DOIUrl":"10.1016/j.bbrep.2026.102457","url":null,"abstract":"<div><h3>Background</h3><div>Abnormal angiogenesis plays vital role in the pathogenesis of adenomyosis (AM). Emerging evidence suggests that exosomes derived from endometrial cells can accelerate the progression of AM. In this study, we aim to investigate the pro-angiogenic role and potential mechanisms of ectopic endometrial mesenchymal stem cells (eMSCs)-derived exosomes (Ec-exo).</div></div><div><h3>Methods</h3><div>MicroRNA sequencing was conducted to identify differentially expressed miRNAs (DE-miRNAs) in exosomes derived from normal eMSCs (N-exo) and Ec-exo. Candidate miRNAs were selected using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-4466 on human umbilical vein endothelial cells (HUVECs) proliferation, invasion/migration, and tube formation were analysed in vitro. The target gene of miR-4466 was predicted via bioinformatics analysis and validated by qRT-PCR, western blotting, luciferase assays, and rescue experiments.</div></div><div><h3>Results</h3><div>We identified 81 up-regulated and 92 down-regulated miRNAs between N-exo and Ec-exo. Among these DE-miRNAs, miR-4466 was the most significantly up-regulated. The internalisation assay demonstrated that exosomal miR-4466 can be internalised by HUVECs. Overexpression or inhibition of miR-4466 significantly promoted or inhibited HUVEC proliferation, invasion/migration, and tube formation. Bioinformatics predictions and luciferase assays revealed that runt-related transcription factor 1 (RUNX1) is a direct target of miR-4466. Moreover, rescue experiments confirmed that RUNX1 overexpression reversed the pro-angiogenic effect of miR-4466 by inhibiting vascular endothelial growth factor A (VEGFA) expression.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates that exosomal miR-4466 derived from ectopic eMSCs promotes angiogenesis by targeting the RUNX1/VEGFA axis in AM. These findings may offer new insights into therapeutic targets and treatment strategies for the anti-angiogenic treatment of AM.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102457"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic functions of polypyrimidine tract-binding protein 1 in breast cancer metabolism and progression","authors":"Manabu Futamura ,&nbsp;Yoshihisa Tokumaru ,&nbsp;Akira Nakakami ,&nbsp;Yoshimi Niwa ,&nbsp;Junichi Mase ,&nbsp;Emiri Sugiyama ,&nbsp;Mai Okawa ,&nbsp;Kana Matsuda ,&nbsp;Ryutaro Mori ,&nbsp;Yukihiro Akao ,&nbsp;Nobuhisa Matsuhashi","doi":"10.1016/j.bbrep.2026.102458","DOIUrl":"10.1016/j.bbrep.2026.102458","url":null,"abstract":"<div><div>Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates alternative splicing and primarily acts as a splicing repressor. Previous studies have shown that PTBP1 is closely linked to cancer metabolism through regulation by miR-133b and miR-124, which inhibit PTBP1 expression and modulate the splicing of the pyruvate kinase muscle (PKM) gene. Increased PTBP1 expression promotes PKM2 production and enhances glycolysis-dependent metabolism, a hallmark of cancer known as the Warburg effect. Clinical and experimental analyses were conducted to investigate the role of PTBP1 in breast cancer (BC). <em>In silico</em> investigations using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets revealed a significant association between PTBP1 overexpression and poor prognosis. <em>In vitro</em>, PTBP1 knockdown in BC cell lines (MCF7, SK-BR-3, and MDA-MB-231) increased PKM1 expression and the PKM1/PKM2 ratio, leading to reduced cell proliferation. ATP production increased in MCF7 and SK-BR-3 cells, but not in MDA-MB-231. Although NADH levels were elevated in MCF7 and MDA-MB-231 cells, lactate accumulation was most prominent in MDA-MB-231 cells. qRT-PCR analysis of surgical BC specimens confirmed significantly higher PTBP1 expression in tumour tissues than in adjacent normal breast tissues, with expression positively correlating with tumour grade. These findings collectively demonstrate that PTBP1 is overexpressed in BC and drives cancer-specific metabolic reprogramming associated with the Warburg effect. Therefore, PTBP1 may act as an oncogenic regulator of breast cancer metabolism and serve as a potential therapeutic target.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102458"},"PeriodicalIF":2.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}