Biochemical and biophysical research communications最新文献

{"title":"Schisandrin A induces osteoblast differentiation to treat glucocorticoid-induced osteoporosis through activating Wnt pathway","authors":"Yuanliang Ai ,&nbsp;Xuehua Xie ,&nbsp;Ying Guo ,&nbsp;Jie Zhao ,&nbsp;Yanfei Xu ,&nbsp;Tao Wang ,&nbsp;Yinghong Huang ,&nbsp;Wenze Huang ,&nbsp;Taohong Ma ,&nbsp;Yan Luo ,&nbsp;Weibo Wen ,&nbsp;Huantian Cui","doi":"10.1016/j.bbrc.2025.152230","DOIUrl":"10.1016/j.bbrc.2025.152230","url":null,"abstract":"<div><div>Schisandrin A (SchA) efficacy in addressing glucocorticoid-induced osteoporosis (GIOP) remains unexplored, and its underlying mechanisms are yet to be clarified. We developed a GIOP mouse model. The efficacy of SchA was assessed comprehensively through micro-CT analysis, biomechanical testing. Using transcriptomic profiling, we investigated the impact of SchA on gene expression in the bone tissue of GIOP mice. Additionally, biochemical assays and Western blot were performed to evaluate SchA's effects on osteogenic growth-related factors in GIOP mice. To complement these findings, we first established an osteoblast injury model to validate the effects of SchA on osteoblast differentiation. We then assessed the activity of the Wnt/β-catenin signaling pathway using a dual luciferase assay and further identified its molecular targets. Our findings demonstrate that SchA intervention significantly improved bone mass parameters, bone mineral density, and bone volume fraction, as well as bone strength indicators in GIOP mice. SchA treatment also elevated serum calcium and phosphorus levels and mitigated pathological damage in the femur. Transcriptomic analysis revealed that SchA upregulated key transcription factors associated with osteoblast differentiatio. Western blot analysis confirmed that SchA intervention increased the expression of key proteins involved in the Wnt signaling pathway. <em>In vitro</em> experiments further validated that SchA upregulated differentiation factors and key Wnt pathway proteins in osteoblasts. The TOP/FOP flash ratio in osteoblasts increased noticeably after SchA treatment, indicating activation of the Wnt/β-catenin signaling pathway. However, when Wnt5a was inhibited using Box5, the regulatory effect of SchA on osteoblast differentiation was abolished. This study comprehensively evaluates the therapeutic effects of SchA on GIOP and suggests that its efficacy likely involves activation of the Wnt signaling pathway in bone cells, thereby promoting osteoblast differentiation and activation, and facilitating bone formation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152230"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338396","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":"The extracellular matrix glycoprotein tenascin-C supports the enriched environment-stimulated neurogenesis in the adult dentate gyrus of mice","authors":"Milena Korenić ,&nbsp;Andrej Korenić ,&nbsp;Vera Stamenković ,&nbsp;Nese Aysit ,&nbsp;Pavle Andjus","doi":"10.1016/j.bbrc.2025.152232","DOIUrl":"10.1016/j.bbrc.2025.152232","url":null,"abstract":"<div><div>The extracellular matrix glycoprotein tenascin C (TnC) is implicated in a variety of processes ranging from cell proliferation and adhesion to synaptic plasticity. The contribution of TnC to neurogenesis related processes in the adult hippocampus, however, remains unclear. To address this question, hippocampal sections were immunostained for the proliferation marker Ki67 and for neuroblast marker doublecortin (DCX). Laser scanning confocal microscopy revealed that TnC - deficiency does not alter either the size of Ki67+ or DCX + cellular populations in the subgranular zone (SGZ) compared to the control animals. Super-resolution Airyscan confocal microscopy enabled the investigation of the complexity of dendritic trees of DCX + cells with the analysis of the dendritic tree complexity parameters. The results show that the dendritic tree complexity of developing neurons is not dependent on the presence of TnC. However, reinforcement of adult neurogenesis by the exposure to enriched environment (EE) revealed that TnC- deficient mice have a reduced number of DCX + cells compared to wild type littermates. This study indicates that TnC might not contribute to the basal levels of adult neurogenesis in the hippocampus, while on the other hand it gains importance in the generation of the positive effect of EE.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152232"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338398","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":"Beyond energy metabolism: ketogenic diet and β-hydroxybutyrate protect against intestinal ischemia-reperfusion injury through anti-inflammatory and barrier-preserving effects","authors":"Fei-xiang Wang ,&nbsp;Na Wei ,&nbsp;Shi-yu Dai ,&nbsp;Xu Zhong ,&nbsp;Guo Mu ,&nbsp;Xin Fan ,&nbsp;Si-rui Chen ,&nbsp;Ye Chen ,&nbsp;Jun Zhou","doi":"10.1016/j.bbrc.2025.152227","DOIUrl":"10.1016/j.bbrc.2025.152227","url":null,"abstract":"<div><div>Intestinal ischemia-reperfusion injury (IRI) is a significant clinical challenge with limited effective treatments. This study investigated the protective effects of ketogenic diet (KD) and β-hydroxybutyrate (BHB) against intestinal IRI using mouse models and intestinal organoids. Following two weeks of KD or BHB administration, mice were subjected to superior mesenteric artery occlusion (60 min) and reperfusion (4 h). Both interventions significantly elevated blood BHB levels and reduced fasting glucose. KD and BHB markedly attenuated intestinal villous damage, preserved epithelial barrier function (E-cadherin, Occludin, ZO-1), maintained mitochondrial integrity, reduced inflammatory cytokines (IL-6, IL-1β, TNF-α), and improved 72-h survival rates, with KD demonstrating superior efficacy. In intestinal organoid oxygen-glucose deprivation models, BHB exhibited differential protective effects at two tested concentrations (2 mM vs. 5 mM), with enhanced protection at the higher concentration on cellular viability, structural integrity, and inflammatory responses. These findings provide the first evidence that ketogenic interventions protect against intestinal IRI through multiple mechanisms including inflammatory suppression and barrier preservation, suggesting potential clinical applications in intestinal IRI prevention and management, though detailed mechanistic elucidation requires further investigation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152227"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313979","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":"The therapeutic effect of topical injection of adipose stem cell-derived extracellular vesicles at different time intervals on wound healing in mice","authors":"Qiang Niu ,&nbsp;Yan Guo ,&nbsp;Zhou Zhang ,&nbsp;Jing Gong ,&nbsp;Fei Liu ,&nbsp;Yu Kong","doi":"10.1016/j.bbrc.2025.152223","DOIUrl":"10.1016/j.bbrc.2025.152223","url":null,"abstract":"<div><div>Adipose-derived stem cell extracellular vesicles (ADEVs) have emerged as a promising biotherapeutic agent, demonstrating efficacy in treating various skin diseases, including wound healing, through local injection. The concentration of ADEVs and the optimal injection interval are critical factors influencing their therapeutic outcomes. However, the optimal dosage and injection intervals for ADEVs in wound healing remain to be elucidated. In this study, we harvested ADEVs from adipose-derived stem cells (ADSCs) of mice and used in vivo imaging to track the local concentration of these vesicles following topical injection. We also evaluated the therapeutic effects of ADEVs on wound healing at different time intervals (4 days, 8 days, and 16 days). Our results indicated that ADEVs injected at concentration over 200 μg/mL persist in skin for more than 7 days. Notably, injection intervals of 4 days and 8 days significantly enhanced wound healing, whereas the 16-day interval did not show such benefits. Additionally, the skin scar tissues in the 4-day and 8-day groups exhibited normal skin structures and appendages, including hair follicles and sebaceous glands. In conclusion, the injection concentration and time intervals influence the outcomes of therapeutic effects of ADEVs under equal total dosages. ADEVs injected at concentration over 200 μg/mL harm the wound healing process with excessive accumulation and unexpected inflammation. Topical injection of ADEVs at a concentration of 50 μg/mL every 4 days or 100 μg/mL every 8 days promote wound healing and skin structure remodeling by regulating angiogenesis-related genes expression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152223"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336037","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":"Short peptides from Late Embryogenesis Abundant (LEA) proteins tune liquid–liquid phase separation and prevent aggregation","authors":"Yinghan Wu ,&nbsp;Yusuke V. Morimoto ,&nbsp;Shinya Ikeno","doi":"10.1016/j.bbrc.2025.152224","DOIUrl":"10.1016/j.bbrc.2025.152224","url":null,"abstract":"<div><div>Short peptides derived from Late Embryogenesis Abundant (LEA) proteins are critically important because they appear to exert their protective functions through liquid–liquid phase separation (LLPS) <em>in vivo</em>. Excitingly, confocal fluorescence microscopy revealed that green fluorescent protein (GFP) exhibited a heterogeneous intracellular distribution in <em>Escherichia coli</em> cells co-expressing LEA peptides. Guided by this observation, we conducted <em>in vitro</em> LLPS assays and found that the LEA-II and LEA-K peptides attenuated segregative LLPS while enhancing solution stability in the associative LLPS mode. These data support our hypothesis that LEA peptides function as molecular shields that suppress protein aggregation, thereby improving heterologous protein expression.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152224"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329703","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":"Fbxl3 deletion mitigates myopathy in mdx mice through upregulation of myogenin","authors":"Min Chen ,&nbsp;Wei He ,&nbsp;Lei Si ,&nbsp;Yanming Wu ,&nbsp;Hua You ,&nbsp;Yangxin Li ,&nbsp;Yao-Hua Song ,&nbsp;Yan Xu","doi":"10.1016/j.bbrc.2025.152220","DOIUrl":"10.1016/j.bbrc.2025.152220","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder with limited therapeutic options, highlighting the urgent need for novel treatment strategies. In this study, we investigated the role of FBXL3 in DMD pathogenesis and assessed its potential as a gene therapy target. Using mdx mice, a well-established preclinical model of DMD, we found that satellite cell-specific deletion of FBXL3 significantly improved muscle pathology and functional performance. FBXL3-deficient mdx mice exhibited increased body and muscle mass, along with enhanced grip strength and endurance capacity. Histological analyses demonstrated a marked increase in both the number and cross-sectional area of centrally nucleated fibers, indicative of enhanced regenerative activity. These changes were associated with elevated myogenin expression and reduced inflammation and fibrosis, suggesting that FBXL3 functions as a negative regulator of muscle repair. Moreover, targeted FBXL3 silencing via adeno-associated virus (AAV) delivery to the gastrocnemius muscle resulted in increased muscle mass and further upregulation of myogenin, supporting its therapeutic relevance. Together, these findings identify FBXL3 as a key modulator of muscle regeneration via repression of myogenin and provide compelling evidence for its inhibition as a promising gene therapy strategy in DMD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152220"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314385","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":"Hyaluronic acid-functionalized PLGA nanoparticles loaded with circSNX6 siRNA overcome sunitinib resistance in renal cell carcinoma","authors":"Yue Gao ,&nbsp;Zhen Li ,&nbsp;Xuelian Wang ,&nbsp;Simeng Chen ,&nbsp;Pengcheng Li ,&nbsp;Xiaowei Tie ,&nbsp;Lu Zhang ,&nbsp;Hongjiang Zhang ,&nbsp;Jin Wang ,&nbsp;Yong Wang","doi":"10.1016/j.bbrc.2025.152226","DOIUrl":"10.1016/j.bbrc.2025.152226","url":null,"abstract":"<div><div>Addressing the challenge of sunitinib resistance in renal cell carcinoma (RCC), while multiple molecular targets have been identified to enhance RCC's response to sunitinib, effective therapeutic strategies remain largely unidentified. Previous studies have highlighted those elevated levels of circular RNA circSNX6, a key regulator of circSNX6/miR-1184/GPCPD1 axis had a critical role in regulation of intracellular lysophosphatidic acid (LPA) levels and sunitinib resistance in RCC. Therefore, there is an urgent need for innovative treatment strategies to combat sunitinib resistance. In this study, we developed hyaluronic acid-modified poly (lactic-co-glycolic acid) nanoparticles (HA-PLGA-NPs) loaded with circSNX6 small interfering RNA (siRNA), designed as a targeted delivery system to overcome drug resistance in RCC. Compared to CD44-negative cells, HA-PLGA-NPs demonstrated markedly improved binding affinity to CD44-positive RCC cells, thereby enhancing their sensitivity to sunitinib. RNA sequencing (RNA-seq) data revealed that circSNX6 knockdown promoted apoptosis, induced mitochondrial changes, and negatively regulated the organization of mitochondrion. In an RCC xenograft model with established sunitinib resistance, the injection of HA-PLGA-NPs carrying circSNX6 siRNA effectively reversed this resistance. These results reveal a novel molecular mechanism through which circSNX6 mediates sunitinib resistance in RCC, and suggest that HA-PLGA-NPs could represent a promising and selective approach for overcoming this resistance.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152226"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365310","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":"Self-association activates ThsB NAD+ hydrolase for defense against phage infection","authors":"Qingdai Luo ,&nbsp;Qiuyang Liu ,&nbsp;Ting Liu ,&nbsp;Xingyu Wang ,&nbsp;Xiaodong Wu ,&nbsp;Qiang Chen ,&nbsp;Yamei Yu","doi":"10.1016/j.bbrc.2025.152217","DOIUrl":"10.1016/j.bbrc.2025.152217","url":null,"abstract":"<div><div>Toll/interleukin-1 receptor (TIR) domain serves as a canonical component in both animal and plant innate immunity pathways and is indicated, in some cases, to mediate nicotinamide adenine dinucleotide (NAD⁺) cleavage via self-association. Recent studies have revealed the involvement of TIR domains in a bacterial anti-phage defense system called Thoeris. The Thoeris system consists of two core proteins, ThsA and ThsB. Phage infection triggers the TIR-containing ThsB to produce an isomer of cyclic ADP-ribose, which is then transferred to and activates ThsA, leading to NAD⁺ depletion and subsequent cell death. However, the mechanism of ThsB activation remains elusive. Here, we present high-resolution crystal structures of <em>E. coli</em> ThsA and ThsB. Notably, an intact NAD⁺ molecule is observed in the active site of ThsB, implying that monomeric ThsB does not possess NADase activity. We demonstrate that ThsB forms 7-fold oligomers through negative staining electron microscopy, suggesting that self-association activates ThsB NAD⁺ hydrolase. Our findings indicate a new TIR self-association assembly in bacterial anti-phage systems.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152217"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313886","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":"Urolithin A attenuates pulmonary fibrosis via the PI3K/AKT/mTOR pathway: Evidence from network pharmacology and experimental validation","authors":"Jiangpo Ma ,&nbsp;Wei Wang ,&nbsp;Kai Gao ,&nbsp;Zhaoxing Dong","doi":"10.1016/j.bbrc.2025.152219","DOIUrl":"10.1016/j.bbrc.2025.152219","url":null,"abstract":"<div><h3>Objective</h3><div>Pulmonary fibrosis(PF) is an abnormal wound-healing response resulting from recurrent alveolar injury, characterized by persistent inflammation and excessive collagen deposition. Given the limited clinical treatment options, novel therapeutic strategies are urgently needed. Urolithin A (UA), a secondary metabolite produced by intestinal microbiota from natural polyphenols, has attracted attention due to its anti-inflammatory, antioxidant, and anti-aging properties. However, the therapeutic efficacy and mechanisms of UA in PF remain unclear. This study aimed to investigate the protective effects and underlying molecular mechanisms of UA in PF.</div></div><div><h3>Methods</h3><div>This study integrated network pharmacology analysis, molecular docking, and in vitro/in vivo experiments to elucidate the anti-fibrotic mechanisms of UA. Firstly, a mouse model of PF was established via intratracheal instillation of bleomycin. Mice in the UA treatment group received daily oral administration of UA (20 mg/kg/day) starting on day 10 post-modeling and continuing until day 21, at which point lung tissues were collected. Histopathological alterations and collagen deposition in the lungs were assessed using Masson's trichrome staining and hydroxyproline content analysis. Furthermore, network pharmacology was employed to predict the potential molecular targets and pathways of UA, which were further validated through molecular docking and in vitro fibroblast experiments to verify the underlying mechanisms.</div></div><div><h3>Results</h3><div>UA treatment significantly alleviated PF in mice, evidenced by reduced collagen deposition, diminished structural damage, and notably decreased excessive extracellular matrix accumulation. Network pharmacology analysis and molecular docking indicated that the PI3K/AKT/mTOR signaling pathway is the primary pharmacological target of UA's anti-fibrotic effect. Further in vitro experiments demonstrated that UA significantly suppressed fibroblast activation by inhibiting AKT1 phosphorylation. Moreover, the inhibitory effects of UA on fibroblasts were reversed upon reactivation of the AKT pathway by the AKT agonist SC79, further confirming the crucial role of the AKT signaling pathway in UA's anti-fibrotic mechanism.</div></div><div><h3>Conclusion</h3><div>UA exerts therapeutic effects on PF by targeting the PI3K/AKT/mTOR pathway, particularly through the inhibition of AKT1 phosphorylation. These findings indicate that UA has potential as a therapeutic candidate for PF and provide a novel perspective for utilizing gut microbiota metabolites in the treatment of fibrotic diseases. Further studies are needed to elucidate the precise mechanisms of UA.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152219"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314386","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":"ZBTB12 promotes breast cancer progression through transcriptional activation of the DNMT3B/ALDH1A2 axis","authors":"Wenshan Zhang ,&nbsp;Yinghui Zhi ,&nbsp;Zhenyu Wu ,&nbsp;Yan Chen ,&nbsp;Liang Feng ,&nbsp;Jing He ,&nbsp;Feng Wang ,&nbsp;Liang Chen ,&nbsp;Huan Liu","doi":"10.1016/j.bbrc.2025.152214","DOIUrl":"10.1016/j.bbrc.2025.152214","url":null,"abstract":"<div><div>Breast cancer (BC) is a prevalent malignant neoplasm. Utilizing the GEPIA database for analysis and subsequent validation via reverse transcription quantitative polymerase chain reaction (RT-qPCR), we identified that aldehyde dehydrogenase 1 family member A2 (ALDH1A2) exhibits reduced expression and heightened methylation in BC, which is associated with an unfavorable prognosis. In vitro cellular assays demonstrated that the overexpression of ALDH1A2 attenuates the proliferative, invasive, and migratory capacities of breast cancer cell lines, concurrently reducing apoptotic rates. Subsequent investigations employing Methylation-Specific PCR and Western blot analysis in breast cancer cells uncovered that DNA methyltransferase 3B (DNMT3B) is implicated in the DNA methylation of ALDH1A2, with the suppression of DNMT3B leading to an elevation in ALDH1A2 protein levels, thereby establishing an inverse relationship between DNMT3B and ALDH1A2. Furthermore, through the prediction of transcription factors binding to the promoter region of DNMT3B, we discerned that zinc fingers and BTB domain containing 12 (ZBTB12) transcriptionally activates DNMT3B, thereby repressing ALDH1A2 expression. Cellular assays revealed that the knockdown of ZBTB12 or the overexpression of DNMT3B correspondingly inhibits or enhances the proliferative, invasive, and migratory capabilities of breast cancer cells, with DNMT3B abrogating the suppressive effects of si-ZBTB12. Our findings elucidate a novel mechanism involving ALDH1A2 in the progression of breast cancer, where ZBTB12 transcriptionally activates DNMT3B, and the ZBTB12-DNMT3B axis orchestrates the methylation and consequent silencing of ALDH1A2.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152214"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321762","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}