Molecular and Cellular Biochemistry最新文献

{"title":"Anti-inflammatory activity of Chlorella polysaccharide AHP.","authors":"Bingfeng Zhou, Su Liang, Jianmei Ou, Changhua Shang","doi":"10.1007/s11010-026-05726-4","DOIUrl":"https://doi.org/10.1007/s11010-026-05726-4","url":null,"abstract":"<p><p>Current medications for inflammatory bowel disease (IBD) are associated with various side effects. Researches had shown that bioactive substances (such as polysaccharides) exhibited anti-inflammatory activity, immunomodulatory activity and the property of the regulation of gut microbiota, which could contribute to the repair of colonic tissue and the improvement of intestinal health. The bioactive substances provided a new direction for developing safe, effective and novel therapeutic strategies. Therefore, the objective of this study was to evaluate the efficacy and safety of Chlorella polysaccharide AHP for the treatment of Caco-2 cell injury and ulcerative colitis in mice. This study investigated the anti-inflammatory activity of polysaccharide extracted from Chlorella (AHP) and its mechanisms through in vitro and in vivo experiments. In vitro, AHP significantly reduced reactive oxygen species (ROS) level, suppressed apoptosis and downregulated the levels of proinflammatory factors in dextran sulfate sodium (DSS)-induced Caco-2 cells, demonstrating antioxidant and anti-inflammatory effects. In vivo, AHP alleviated pathological damage of colon, decreased oxidative stress and levels of pro-inflammatory cytokines, enhanced expression of tight junction proteins and repaired intestinal mucosal barrier in mice with DSS-induced colitis. Furthermore, AHP modulated gut microbiota composition and levels of related metabolites, contributing to its anti-inflammatory activity through microecological regulation. These findings indicated that AHP mitigated DSS-induced cell injury and colonic damage via multiple pathways, confirming its potent anti-inflammatory properties through in vitro and in vivo experiments. This study provided important theoretical basis for exploring new treatments of IBD with bioactive substance AHP and developing functional foods based on AHP.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laminin-triggered integrin signaling potentiates γ-enolase-induced neurite outgrowth.","authors":"Selena Horvat, Urša Pečar Fonović, Janko Kos, Anja Pišlar","doi":"10.1007/s11010-026-05755-z","DOIUrl":"https://doi.org/10.1007/s11010-026-05755-z","url":null,"abstract":"<p><p>Neurite growth is regulated by trophic support and the extracellular matrix (ECM). γ-Enolase, a neuron-specific enolase isoform, promotes neurite outgrowth through neurotrophic-like activity, but the contribution of ECM engagement and integrin signaling remains unclear. Here, we examined the role of laminin, collagen, and poly-L-lysine in γ-enolase peptide-induced neuritogenesis in neuroblastoma SH-SY5Y and pheochromocytoma PC12 cells. Treatment with a synthetic C-terminal γ-enolase peptide (γ-Eno) rapidly induced neurite outgrowth and actin remodeling, with laminin providing the strongest enhancement, particularly in SH-SY5Y cells. γ-Eno increased surface expression of β1 integrin and, to a lesser extent, α1 integrin, alongside a stronger neurite response on laminin. In laminin-coated cells, actin remodeling was evident within 3 h, followed by increased neurite formation at 24 h and significant neurite elongation at 48 h. Mechanistically, γ-Eno induced focal adhesion kinase (FAK) phosphorylation, which was significantly increased in both cell types on laminin and collagen. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was cell type- and ECM-dependent, whereas Akt phosphorylation increased significantly in SH-SY5Y cells but did not change markedly in PC12 cells. Integrin blockade with GRGDS attenuated γ-Eno-induced neurite outgrowth, MAP2 expression, and FAK phosphorylation. GRGDS also reduced Akt phosphorylation in SH-SY5Y cells and attenuated ERK1/2 phosphorylation in PC12 cells, supporting cell type-specific downstream signaling. These findings show that laminin-mediated integrin signaling enhances γ-enolase-induced neurite outgrowth and is associated with integrin-dependent FAK activation, with ERK1/2 and Akt contributing in a context-dependent manner.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of receptor-interacting protein kinases (RIP1 and RIP3) in the therapeutic effect of thymoquinone against rat testis ischemia/reperfusion.","authors":"Hatice Gülmez, Hüseyin İlbasmış, Hilal Akalın, Mustafa Ermiş, Derya Karabulut","doi":"10.1007/s11010-026-05756-y","DOIUrl":"https://doi.org/10.1007/s11010-026-05756-y","url":null,"abstract":"<p><p>Torsion-induced ischemia causes lipid peroxidation in tissue, increases membrane permeability, and induces irreversible necroptosis in cells. The aim was to investigate the effects of thymoquinone (THQ) on receptor-interacting serine-threonine kinases (RIP1 and RIP3) after testicular torsion-induced ischemia/reperfusion (I/R). Control, ischemia/reperfusion (I/R), thymoquinone (THQ) 10 mg/kg and ischemia/reperfusion + thymoquinone (I/R+THQ). At the end of the experiment, spermiogram, histological and immunohistochemical, gene expression and biochemical analyses were performed on testicular tissue by collecting blood samples. Motility, testicular tissue seminiferous tubule epithelium thickness, tubule diameter and JTBS decreased in the I/R group compared to the Control and THQ groups.Both gene expression and immunoreactivity intensities of RIP1 and RIP3 increased in I/R. Furthermore, glial cell-derived neurotrophic factor (GDNF) and androgen-binding protein (ABP) decreased, steroidogenic acute regulatory protein (StAR), blood testosterone, and luteinizing hormone (LH) increased, and follicle-stimulating hormone (FSH) remained unchanged. THQ had a regulatory effect on all parameters. In addition to histopathological findings in testicular tissue, changes in RIP1, RIP3, GDNF, and StAR expression after I/R caused damage to both spermatogenic and non-spermatogenic tissue cell lines. Furthermore, changes in hormone levels indicate tissue dysfunction. The results reveal novel findings suggesting that THQ, applied after I/R, may be an effective compound for improving the structural and functional integrity of tissue; however, these findings need to be confirmed using various techniques with different application times and doses.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, green synthesis, and anticancer evaluation of novel sulfaguanidine-based heterocycles as multi-target inhibitors of the VEGFR-2/PI3K/AKT/mTOR pathway.","authors":"Walaa K Elabd, Kurls E Anwer, Marwa Sharaky, Rehab Abdel-Hameed","doi":"10.1007/s11010-026-05727-3","DOIUrl":"https://doi.org/10.1007/s11010-026-05727-3","url":null,"abstract":"<p><p> The pursuit of multi-target anticancer agents is a strategic approach to overcome drug resistance and improve selectivity. This study focuses on the design of novel heterocyclic compounds incorporating a sulfaguanidine moiety, targeting key pathways in cancer progression. A novel diazonium intermediate was synthesized from sulfaguanidine and used to prepare a series of pyrimidine and triazine derivatives 3-8 via both conventional and eco-friendly microwave techniques. All compounds were characterized by spectroscopic methods. The cytotoxic activity was evaluated against five human cancer cell lines (HEPG2, MCF7, A431, A375, and A549) and normal HSF fibroblasts. The mechanism of the lead compounds 3 and 4 was investigated through cell cycle analysis, qPCR analysis of VEGFR-2, PI3K, AKT, mTOR, Caspase-3, and CDC42 genes, and comprehensive molecular docking studies against the corresponding protein targets. ADMET profiles were also predicted. Microwave synthesis significantly improved reaction efficiency. Compounds 3 and 4 exhibited the most potent and selective cytotoxicity, with compound 4 showing activity against A431 cells (IC₅₀ = 4.87 µM). Mechanistic studies revealed compound 3 induced G2/M arrest, while Compound-4 caused G1 arrest. QPCR analysis confirmed significant downregulation of VEGFR-2, PI3K, AKT, mTOR, and CDC42, alongside upregulation of pro-apoptotic Caspase-3. Docking studies supported strong binding affinities to VEGFR-2, PI3K, AKT, and mTOR, correlating with the biological data. The integrated chemical and biological approach identified compounds 3 and 4 as promising multi-target agents. Their ability to disrupt angiogenesis, survival signaling, and cell cycle progression, while inducing apoptosis, highlights their potential as lead compounds for further anticancer development.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum exosomal miRNA signature in hypertension: an exploratory study integrating with comparative analysis of the GEO database.","authors":"Dongling Zhong, Yue Zhang, Tianyu Liu, Yuxi Li, Xiaobo Liu, Yuan Chen, Qian Liang, Jiayi Chen, Congjie Lei, Rongjiang Jin, Juan Li","doi":"10.1007/s11010-026-05744-2","DOIUrl":"https://doi.org/10.1007/s11010-026-05744-2","url":null,"abstract":"<p><p>Essential hypertension (EH) remains a leading cause of mortality worldwide. Exosome-carried microRNAs (miRNAs) play a pivotal role in the pathogenesis of EH. In this exploratory study, we aimed to characterize the serum exosomal miRNA expression profile in patients with EH and to investigate the potential functional relevance of differentially expressed (DE) miRNAs, aiming to provide preliminary evidence for future mechanistic investigations. Serum exosomes were isolated from patients with EH and healthy controls, followed by small RNA sequencing. Differentially expressed (DE) miRNAs were identified and further subjected to bioinformatic target gene prediction. To elucidate the potential biological functions of these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Additionally, a comparative analysis of the DE miRNAs was conducted using an independent dataset from the Gene Expression Omnibus (GEO) database. Six significantly downregulated miRNAs (hsa-miR-16-5p, hsa-miR-652-3p, hsa-miR-93-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-193a-5p) were identified in 20 hypertensive patients compared with 10 healthy controls. GO and KEGG analyses revealed that the predicted target genes of these miRNAs were significantly enriched in biological processes related to neuronal function, protein homeostasis, and cell cycle regulation, and were primarily involved in MAPK, Hippo, p53, and TGF-β signaling pathways. Notably, comparative analysis of the GEO dataset demonstrated a distinct expression profile between exosomal and total plasma miRNAs, underscoring the unique value of exosome-specific analysis. This exploratory study identified six serum exosomal miRNAs as candidate biomarkers for hypertension, with predicted targets enriched in MAPK and TGF‑β pathways. The exosomal signature was distinct from total plasma miRNA profiles, suggesting that exosomal miRNAs may carry disease‑specific signals. However, given the limited sample size and exploratory nature of this study, these findings are preliminary and require validation in larger cohorts.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic acid partially attenuates thiomersal-associated oxidative, apoptotic, and CREB/BDNF-related alterations in rat hippocampal and prefrontal cortex tissues and systemic inflammatory responses.","authors":"Murat Celebi, Cagla Celebi","doi":"10.1007/s11010-026-05752-2","DOIUrl":"https://doi.org/10.1007/s11010-026-05752-2","url":null,"abstract":"<p><p>Thiomersal (THIM), an organomercury preservative, has been associated with oxidative stress-related neurotoxicity. This study investigated the effects of gallic acid (GA) on THIM-associated oxidative, apoptotic, and CREB/BDNF-related molecular alterations in brain tissue and systemic inflammatory responses in rats. Twenty-eight male Wistar albino rats were assigned to Control, THIM, GA, and THIM+GA groups (n = 7/group). THIM (25 µg/kg, intraperitoneally) was administered at 10-day intervals, whereas GA (50 mg/kg/day, oral gavage) was given for 20 consecutive days. MDA, SOD, CAT, and GSH were measured in combined hippocampal and prefrontal cortex homogenates; serum MDA, IL-1β, IL-6, and TNF-α were also assessed. Bax, Bcl-2, Casp-3, CREB, and BDNF mRNA expression was analyzed by RT-qPCR. THIM increased tissue MDA (0.44 ± 0.06 vs. 1.06 ± 0.15 nmol/mg protein, p < 0.0001) and serum TNF-α (93.9 ± 9.6 vs. 171.3 ± 8.8 ng/L, p < 0.0001) and reduced BDNF mRNA expression (1.01 ± 0.15 vs. 0.41 ± 0.17, p = 0.0001). In THIM-exposed animals, GA reduced tissue MDA and serum TNF-α and increased BDNF expression (all p < 0.05). Significant THIM × GA interactions were identified for tissue CAT, GSH, MDA, Bax/Bcl-2 ratio, BDNF, and serum MDA, IL-1β, IL-6, and TNF-α. Simple-effects analyses indicated that GA effects were mainly evident during THIM exposure. These findings suggest that GA partially attenuates THIM-associated oxidative and apoptosis-related molecular alterations, systemic inflammatory responses, and BDNF-related transcriptional changes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANKRD28 interacts with DOCK180 to activate Rac1-STAT3-Myc signaling and sustain stemness of CD34⁺ leukemia stem cells in acute myeloid leukemia.","authors":"Xiaoyan Zheng, Yue Du, Xiaohui Zhang, Huachao Zhu","doi":"10.1007/s11010-026-05749-x","DOIUrl":"https://doi.org/10.1007/s11010-026-05749-x","url":null,"abstract":"<p><p>Leukemia stem cell (LSC) stemness maintenance is a core cause of relapse and therapeutic resistance in acute myeloid leukemia (AML). ANKRD28, an ankyrin repeat domain‑containing gene, has been implicated in malignant phenotypes across various tumors, but its role in regulating AML LSC stemness remains unclear. GEO datasets (GSE9476, GSE30029) and public databases (GEPIA2, TIMER, CCLE) were analyzed to characterize ANKRD28 expression and prognostic relevance in AML and LSCs. ANKRD28 expression in CD34⁺ LSCs from newly diagnosed AML patients was assessed by RT‑qPCR and Western blot. Effects on proliferation, cell cycle, apoptosis, and stemness markers were evaluated using colony formation, CCK‑8, EdU incorporation, flow cytometry, and Western blot. A patient‑derived xenograft (PDX) model was used to assess in vivo tumorigenic capacity. Downstream signaling was explored via GEPIA2 correlation analysis, Western blot, and rescue experiments. Co‑immunoprecipitation (Co‑IP), Rac1 activity assays, and nuclear‑cytoplasmic fractionation were performed to elucidate the underlying mechanism. ANKRD28 was overexpressed in AML tissues, CD34⁺ cells, and CD34⁺‑enriched cell lines, and was associated with FLT3 mutations, relapse, and poor prognosis. Its expression was positively correlated with LSC markers. CD34⁺ANKRD28⁺ cells exhibited greater colony‑forming capacity than CD34⁺ANKRD28^- cells. ANKRD28 knockdown inhibited LSC proliferation, induced apoptosis, caused cell cycle arrest, and downregulated stemness markers, whereas overexpression exerted opposite effects. In vivo, ANKRD28 knockdown prolonged survival, reduced LSC infiltration, and alleviated histopathological damage. Mechanistically, ANKRD28 directly bound DOCK180, activated Rac1, promoted STAT3 nuclear translocation and transcriptional activation, and upregulated Myc expression. ANKRD28 is overexpressed in AML CD34⁺ LSCs and sustains stem cell‑like properties via the DOCK180‑Rac1‑STAT3‑Myc axis, serving as a potential therapeutic target for AML.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The adaptor protein ARAP contributes to Akt-dependent NF-κB p50 activation and inflammatory cytokine production in dendritic cells.","authors":"Chohee Park, Jong Ran Lee","doi":"10.1007/s11010-026-05751-3","DOIUrl":"https://doi.org/10.1007/s11010-026-05751-3","url":null,"abstract":"<p><p>Adaptor proteins play critical roles in determining the specificity of innate immune signaling pathways. Here, we report that a previously uncharacterized adaptor protein, ARAP (activation-dependent, raft-recruited ADAP-like phospho-protein), is critical for lipopolysaccharide (LPS)-induced cytokine production in dendritic cells (DCs). Bone marrow-derived DCs (BMDCs) isolated from ARAP knockout (ARAP-KO) mice exhibited a significant reduction in proinflammatory cytokine production following LPS stimulation. Mechanistically, ARAP-KO-derived BMDCs displayed normal activation of mitogen-activated protein kinases and inhibitor of κBα (IκBα) degradation, along with preserved nuclear translocation of nuclear factor-κB (NF-κB) p65. However, the nuclear translocation of the NF-κB p50 subunit was markedly impaired. Concomitantly, LPS-induced Akt phosphorylation was attenuated in ARAP-KO-derived BMDCs. Pharmacological inhibition of Akt in wild-type BMDCs phenocopied the defect in p50 nuclear translocation. These findings reveal a non-canonical mechanism in which ARAP is required for p50 nuclear translocation in an Akt-dependent pathway, independent of classical IκB kinase-IκB signaling, adding mechanistic insight into innate immune signaling.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytoestrogens and related microbial metabolites remodel aberrant prostate transcriptomic profiles generated upon exposure to oxidative stress.","authors":"Jiaxi Zhang, Arian Abolhassani, Cayla Boycott, Marco Tello-Palencia, Katarzyna Papierska, Ali Khan, Maidinai Sabier, David D Kitts, Barbara Stefanska","doi":"10.1007/s11010-026-05750-4","DOIUrl":"https://doi.org/10.1007/s11010-026-05750-4","url":null,"abstract":"<p><p>Dietary phytoestrogens, including pterostilbene (PTS) from berries and genistein (GEN) from soybeans, exert anti-oxidant and anti-inflammatory effects in prostate cancer. However, the specific actions in regulation of cell biology and homeostasis in normal prostate epithelial cells remain unknown and a prominent research gap refers to the effects of related microbial metabolites of phytoestrogens. We therefore explored effects of distinct phytoestrogens, PTS and GEN, and PTS microbial metabolite, pinostilbene (PNS), in healthy cells with disrupted homeostasis. Human RWPE-1 prostate epithelial cells were treated with 100 µM concentration of hydrogen peroxide (H₂O₂). The H₂O₂-challenged cells were then exposed to phytoestrogens, followed by RNA sequencing. Transcriptomics revealed 1,770 differentially expressed genes (DEGs) upon H₂O₂ exposure. Upregulated genes were functionally implicated in immune signaling and inflammatory pathways, whereas downregulated genes were linked to autophagy, homeostasis, and cellular architecture. A quantitative metric termed the Weighted Recovery Ratio (WRR) was developed to quantify the extent that the treatment reversed gene expression change induced upon H₂O₂ challenge. WRR indicated that PNS recovered the highest number of H₂O₂-responsive genes. Among all PTS and PNS DEGs, 47% and 69%, respectively, constituted partially or fully recovered H₂O₂-responsive genes. This fraction was only 9% for GEN. PTS and PNS, but not GEN, recovered genes involved in DNA methylation/demethylation, which suggests restoration of DNA methylation equilibrium that was disrupted by H₂O₂. Our findings provide a novel tool to quantify the relative efficacy of phytoestrogens in attenuating alterations caused by an oxidative stressor. We present evidence for differential action of phytoestrogens with distinct chemical structures and for more potent action of microbial metabolites derived from phytoestrogens.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3‑mediated OTUB1 sustains PD‑L1 protein stability via deubiquitination and promotes immune evasion in oral squamous cell carcinoma.","authors":"Dongbin Chen, Qinghua Liu, Qisong Wang, Juncai Lin, Jie Wang","doi":"10.1007/s11010-026-05732-6","DOIUrl":"https://doi.org/10.1007/s11010-026-05732-6","url":null,"abstract":"<p><p>Immune evasion facilitates the progression of oral squamous cell carcinoma (OSCC). This study investigates how METTL3-mediated OTUB1 modulates PD-L1 ubiquitination and promotes immune evasion in OSCC. OTUB1 expression was analyzed in tumor and adjacent normal tissues from OSCC patients. OTUB1 knockdown experiments were performed in HN-6 cells. The relationship between OTUB1 and PD-L1 was detected. OTUB1-knockdown HN-6 cells were co-cultured with activated PBMCs, and tumor immunity was subsequently assessed. Tumor growth and immunity were observed in a mouse model injected with HN-6 cells transfected with si-OTUB1 and oe-PD-L1. The mechanistic interaction among METTL3, YTHDF1, and OTUB1 was determined, as well as their action in mouse tumor models. OTUB1 was upregulated in OSCC and correlated with poor prognosis. Knocking down OTUB1 directly increased PD-L1 ubiquitination levels, downregulated PD-L1 protein abundance, and weakened the binding between tumor cells and PD-1. OSCC cells with OTUB1 knockdown were co-incubated with PBMCs, resulting in enhanced apoptosis of OSCC cells, increased CD4⁺/CD8⁺ T cell infiltration, reduced FoxP3⁺ Tregs, exhausted CD8⁺ T cell subsets, and elevated GzmB/IFN-γ production. METTL3 mediated m⁶A modification of OTUB1 mRNA, which enhanced the stability of OTUB1 mRNA and upregulated OTUB1 expression through the reader protein YTHDF1. In vivo experiments confirmed that METTL3 promoted OSCC progression and immune evasion via m⁶A-dependent OTUB1 regulation and subsequent PD-L1-mediated CD8⁺ T cell suppression. METTL3 stabilizes OTUB1 mRNA through m⁶A methylation, upregulates PD-L1 expression, and promotes immune evasion, thereby accelerating OSCC progression.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}