International Journal of Biological Sciences最新文献

{"title":"Integrated single-cell TCR analysis across tissue identifies GZMK⁺CD8⁺ T cells promoting fibrosis via TGF-β signalling in IPF.","authors":"Bingqing Yue, Shuliang Jing, Qiaxuan Li, Guoyu Xie, Juan Chen, Tao Yan, Ganggui Zhu, Bin Huang, Jin Zhao, Xiucheng Yang, Jian Huang, Pan Yin, Qifeng Yao, Huijing Yang, Fei Gao, Jun Yang, Man Huang, Jingyu Chen","doi":"10.7150/ijbs.134974","DOIUrl":"10.7150/ijbs.134974","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with progressive scarring and an unknown aetiology, but the cross-tissue immune network remains poorly understood. Here, we performed paired single-cell RNA sequencing and T cell receptor profiling of lung, mediastinal lymph node, and peripheral blood samples from patients with severe IPF. We identified a GZMK⁺CD8⁺ T cell subset enriched in fibrotic lung tissue with an inflammatory, low-cytotoxic phenotype, and a clonally related CD8_HSPA1A population enriched in lymph nodes, suggesting a cross-tissue clonal connection. Higher GZMK⁺CD8⁺ T cell signatures were associated with worse survival and impaired lung function. Functionally, GZMK overexpressing CD8⁺ T cells promoted fibroblast-to-myofibroblast differentiation and proliferation through TGF-β1/Activin A signalling, whereas GZMK knockdown attenuated these responses. Importantly, genetic ablation of GZMK markedly reduced collagen deposition and lung fibrosis in bleomycin-induced mice. Furthermore, inhibition of TGFβR1/ALK4 using the inhibitor TEW-7197 effectively suppressed fibroblast activation in vitro and significantly attenuated pulmonary fibrosis in bleomycin-induced mice. Together, these findings suggest a potential profibrotic immune-stromal circuit in severe IPF in which GZMK⁺CD8⁺ T cells promote fibroblast activation through TGF-β1/Activin A signalling, highlighting this pathway as a potential therapeutic target.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7862-7886"},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting tubular NAT10 ameliorates the renal Tubulointerstitial Fibrosis in Obstructive and Folic Acid-Induced Nephropathy.","authors":"Qin Kang, Lin Yin, Chenkai Wu, Wende Yan, Sai Peng, Jinfang Lu, Dongshan Zhang","doi":"10.7150/ijbs.135844","DOIUrl":"10.7150/ijbs.135844","url":null,"abstract":"<p><p>Renal tubulointerstitial fibrosis (TIF) represents a common pathological hallmark during the progression of chronic kidney disease (CKD). NAT10, an RNA acetyltransferase, catalyzes N4-acetylcytidine modification of mRNA and has been associated with multiple pathological events, including bladder cancer progression, tumor metastasis, and cardiac remodeling. Nevertheless, NAT10's precise function and underlying molecular mechanisms in TIF remain inadequately elucidated. In this investigation, transforming growth factor-β1 (TGF-β1) was found to promote NAT10 expression in BUMPT cells via p53 upregulation. Functionally, NAT10 was demonstrated to regulate FN, Collagen I, and Collagen III expression triggered by TGF-β1 stimulation. Mechanistically, NAT10 enhanced Spred2 expression by promoting acetylation-dependent mRNA stability, which subsequently activated the JNK and ERK/TGF-β signaling pathways. Furthermore, a renal tubular epithelial cell-specific NAT10 knockout mouse model was established, and NAT10 deficiency's influence on TIF progression was examined using unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced renal fibrosis models. The findings indicated that tubular epithelial-specific NAT10 deletion markedly alleviated UUO- and FA-induced renal TIF via inhibiting Spred2/JNK and ERK/TGF-β signaling. Finally, 5-Fluorouridine, a potent ribozyme self-cleavage inhibitor, was observed to attenuate UUO- and FA-induced renal TIF by targeting NAT10. Collectively, a previously unrecognized p53/NAT10/Spred2/JNK and ERK/TGF-β regulatory axis driving renal TIF is identified, and 5-Fluorouridine represents a viable therapeutic intervention for renal TIF.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7667-7685"},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tubular NAT10 Promotes the Secretion of TGF-β and Lactate to Drive Fibroblast Activation in Diabetic Kidney Disease.","authors":"Jinfang Lu, Yuqing Feng, Xujun Peng, Zijin He, Zhou Li, Ao Jia, Yaohui Bao, Lingui Xie, Renchun Wang, Wenbo Zhang, Qin Kang, Yanyan Zhou, Cheng Wang, Hongquan Peng, Huiling Li, Dongshan Zhang","doi":"10.7150/ijbs.140281","DOIUrl":"10.7150/ijbs.140281","url":null,"abstract":"<p><p>In advanced diabetic kidney disease (DKD), tubulointerstitial fibrosis (TIF) is a key histopathological lesion accompanying progressive renal functional decline. However, the tubular mechanisms that drive tubulointerstitial fibrogenesis remain incompletely understood. N-acetyltransferase 10 (NAT10) mediates mRNA N4-acetylcytidine (ac4C) modification, but its role and therapeutic potential in DKD are unknown. We investigated NAT10 regulation and function using cultured tubular cells, diabetic mouse models, patient kidney specimens, and tubule-specific Nat10 knockout mice, together with pharmacological treatment using guanosine diphosphate disodium salt. High glucose or diabetes increased tubular NAT10 abundance in cultured cells, mouse kidneys, and human DKD tissues through activation of NF-κB signaling. Mechanistically, NAT10 in tubular cells stabilized <i>Brd4</i> and <i>Pfkm</i> mRNAs through ac4C modification, activating the STAT3/TGF-β and lactate/H3K18 lactylation pathways. These pathways synergistically promoted fibroblast activation through NOTCH/SMAD3 signaling and formed a positive feedback loop with NF-κB. Tubule-specific <i>Nat10</i> deletion reduced <i>Brd4</i> and <i>Pfkm</i> expression, suppressed the associated signaling cascades, and mitigated kidney fibrosis in the DKD model. Consistently, guanosine diphosphate disodium salt alleviated renal injury and fibrosis in <i>db/db</i> mice. Thus, NAT10 drives tubular fibrosis through ac4C-dependent profibrotic signaling, supporting NAT10 inhibition as a potential therapeutic strategy for DKD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7737-7759"},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAF-derived BHB modulates FXR1-Kbhb and NK-cell lipid metabolism in osteosarcoma.","authors":"Yihan Yu, Wei Wu, Anzhen Ju, Lei Zhao, Guohui Liang, Yun Liu, Zengwu Shao, Feifei Pu, Binlong Zhong, Fengxia Chen, Jianxiang Liu, Zhicai Zhang","doi":"10.7150/ijbs.128764","DOIUrl":"10.7150/ijbs.128764","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents and is characterized by high aggressiveness and poor prognosis. Although surgery and chemotherapy have improved overall survival, outcomes for relapsed or metastatic disease remain extremely poor, thus underscoring the urgent need for novel therapeutic strategies. Natural killer (NK) cells are key cytotoxic effectors in tumor immunity, but their function is profoundly suppressed within the OS tumor microenvironment. Furthermore, the role of cancer-associated fibroblasts (CAFs) in mediating NK-cell dysfunction through metabolic regulation remains insufficiently understood. We established coculture systems of NK cells, OS cells, and CAFs and assessed NK-cell activation and cytotoxicity by using functional assays, flow cytometry, and immunofluorescence. Metabolic profiling was performed with extracellular acidification rate, oxygen consumption rate, reactive oxygen species detection, MitoTracker staining, and electron microscopy. Integrated proteomics and mechanistic studies were used to identify CAF-derived metabolites and their effects on NK-cell metabolism. CAFs markedly impaired NK-cell recognition and cytotoxicity toward OS cells, accompanied by metabolic reprogramming characterized by enhanced glycolysis, increased reactive oxygen species production, and reduced mitochondrial activity. Multiomics and functional analyses identified β-hydroxybutyrate (BHB) as a key CAF-derived metabolite that contributed to reduced NK-cell FAO and effector function. BHB treatment increased FXR1 Kbhb and reduced FAO, cytokine secretion, and tumor-cell killing, whereas FXR1 K56 mutation attenuated these functional changes. <i>In vivo</i>, CAF-CM treatment was accompanied by elevated circulating BHB, reduced NK-cell activation, and accelerated tumor growth. Targeting the CAF-BHB- FXR1 axis may represent a promising therapeutic strategy to restore NK cell-mediated antitumor immunity and improve treatment outcomes.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7714-7736"},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies.","authors":"Mengyuan Gao, Chongjin Zhong, Jiajia Shen, Sainan Peng, Xue Zhou, Qiuhong Shen, Cheng Qian, Xinming Yang, Yuxuan Gong, Kang Zhang, Yin Lu, Xiaodong Shu, Yang Zhao","doi":"10.7150/ijbs.133661","DOIUrl":"10.7150/ijbs.133661","url":null,"abstract":"<p><p>Vascular aging is a dynamic biological process contributing to systemic organismal decay. This review elucidates the heterogeneous cellular phenotypes and microenvironmental remodeling across macrovascular and microvascular beds. These multifaceted pathological shifts are integrated into a unified tripartite framework of twelve hallmarks of vascular aging. These specific molecular dimensions ultimately dictate the clinical divergence between early vascular aging (EVA) and the supernormal vascular aging (SUPERNOVA) phenotype. Furthermore, vascular aging serves as a primary key driver of distant organ dysfunction. Based on these mechanistic insights, we summarize current behavioral and pharmacological senotherapeutic strategies targeting aged blood vessels. This systematic analysis provides critical benchmarks for deciphering vascular senescence and promoting healthy longevity.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7686-7713"},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomilin Rewires mTOR-Driven Immunometabolism via DDIT4 to Restrain Psoriasis.","authors":"Ha Eun Kim, Seung Taek Lee, Hee-Suk Park, Hyun-Su Lee, Jong Yeong Lee, Dae-Ki Kim, Si-Gyun Roh, Kyung-Hwa Nam, Sang-Hyun Kim, Jin Kyeong Choi","doi":"10.7150/ijbs.133330","DOIUrl":"10.7150/ijbs.133330","url":null,"abstract":"<p><p>Nomilin, a citrus-derived limonoid belonging to the tetranortriterpenoid family, has been reported to exert anti-inflammatory and antioxidant effects; however, its therapeutic relevance and underlying mechanisms in psoriasis remain unclear. Here, we investigated the effects of nomilin in 12-O-tetradecanoylphorbol-13-acetate (TPA)- and imiquimod (IMQ)-induced psoriasis-like mouse models, IL-17A-stimulated primary human keratinocytes, Th17-polarized CD4⁺ T cells, and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Nomilin markedly alleviated epidermal hyperplasia and inflammatory symptoms, suppressed pro-inflammatory cytokines and psoriasis-associated mediators, and reduced the expansion of inflammatory myeloid and Th1/Th17 cells in lesional skin. Mechanistically, nomilin decreased glucose uptake, glycolytic activity, oxidative phosphorylation, mitochondrial mass, and mitochondrial ROS production, thereby preventing metabolic overactivation and mitochondrial dysfunction. At the molecular level, nomilin upregulated DDIT4 and inhibited mTOR signaling, as evidenced by reduced phosphorylation of mTOR, RAPTOR, p70S6K, and 4EBP1. Genetic silencing of DDIT4 abrogated the anti-inflammatory and metabolic effects of nomilin in keratinocytes, while skin-specific DDIT4 knockdown markedly attenuated its therapeutic efficacy <i>in vivo</i>, demonstrating an essential role for DDIT4 in nomilin-mediated mTOR suppression. Furthermore, molecular docking and cellular thermal shift assay (CETSA) analyses revealed a direct interaction between nomilin and DDIT4. In addition, nomilin suppressed Th17 differentiation and reduced TNF-α-, IFN-γ-, and IL-17A-producing CD4⁺ T cells in PBMCs from patients with psoriasis. Collectively, these findings identify nomilin as a modulator of the DDIT4-mTOR axis that alleviates psoriasis-like inflammation through the rewiring of pathogenic immunometabolic programs and highlight its potential as a therapeutic strategy for psoriasis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7512-7532"},"PeriodicalIF":11.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent protective responses of taurine in ameliorating radiation-induced intestinal injury: gut microbiota reprogramming in males and estrogen-dependent immunity in females.","authors":"Xudong Ding, Jia Du, Zhaoyu Wang, Lu Lu, Saijun Fan","doi":"10.7150/ijbs.137118","DOIUrl":"10.7150/ijbs.137118","url":null,"abstract":"<p><p>Radiation-induced intestinal injury (RIII) limits abdominal and pelvic radiotherapy. Safe and effective radioprotectors that do not protect tumors remain an unmet need. Here, we examined the radioprotective effect of taurine (Tau) in mice subjected to whole-abdominal irradiation (WAI) and whether this effect depends on sex. Tau treatment improved post-irradiation survival, preserved intestinal stem cells, prevented mucosal barrier breakdown, and reduced systemic inflammation. These effects, however, were sex-dependent. In male mice, Tau altered the gut microbiota, increasing <i>Ligilactobacillus</i> abundance and shifting arginine and proline metabolism. In female mice, Tau maintained circulating estrogen levels, which in turn upregulated AICDA expression and enhanced IgA-mediated intestinal immunity. Under the specific dosing regimens and radiation parameters utilized in this study, Tau neither altered baseline tumor progression nor compromised the tumor response to irradiation. We conclude that Tau protects against RIII through sex-specific mechanisms, microbiota reprogramming in males and estrogen-AICDA-IgA signaling in females, without compromising the antitumor efficacy of radiotherapy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7628-7643"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative extracellular vesicles reshape systemic aging: lessons from antler stem cells.","authors":"Seung-Jae Lee, Jaehoon Bae, Ye Ji Cheon, Eun-Kyung Kim","doi":"10.7150/ijbs.140033","DOIUrl":"10.7150/ijbs.140033","url":null,"abstract":"","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7606-7609"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Microbial Metabolite IDA Sensitizes Tumor Cells to ARF1 Inhibition by Inducing SVIL-dependent Senescence.","authors":"Menglin Huang, Xuan Wang, Yanfeng Jiang, Jincheng Li, Binliu Hu, Yuetong Wang, Steven X Hou","doi":"10.7150/ijbs.133716","DOIUrl":"10.7150/ijbs.133716","url":null,"abstract":"<p><p>While pharmacological inhibition of ARF1 exhibits robust antitumor activity, its therapeutic efficacy is constrained by tissue-specific limitations. To augment the clinical potential of our developed ARF1 inhibitor, DU102, we pursued a strategy of senescence induction. A screen for endogenous senescence-inducing metabolites identified trans-3-indoleacrylic acid (IDA), a microbiota-derived metabolite, as a potent senescence inducer. We demonstrate that IDA acts through targeting supervillin (SVIL), leading to subsequent enhancement of the expression of the senescence-associated enzyme galactosidase beta 1 (GLB1). <i>In vivo</i>, IDA enhanced the antitumor efficacy of DU102 through senescence-dependent sensitization, overcoming tissue-restricted resistance and achieving potent tumor suppression. Further analysis revealed that this combination remodels the tumor microenvironment by coordinately regulating tumor-associated macrophages through different predominant mechanisms: IDA predominantly promotes M1-like polarization via TNFα, whereas ARF1 inhibition primarily drives macrophage expansion through CSF2 upregulation. Our work unveils a novel metabolite-regulated senescence pathway and establishes a rational combination therapy that effectively co-opts tumor-associated macrophages (TAMs) for cancer treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7585-7605"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SH2B3 Promotes PD-L1-Mediated Immune Evasion in Glioblastoma via BRCC3-Dependent IGF2BP2 Stabilization.","authors":"Rongqing Li, Jiahui Wang, Xiangrui Meng, Jiahua Pan, Xin Chen, Xin Pan, Wei Li, Shigang Qiao, Li Qian","doi":"10.7150/ijbs.134558","DOIUrl":"10.7150/ijbs.134558","url":null,"abstract":"<p><p>Glioblastoma (GBM) is characterized by aggressive progression and profound immune evasion, yet the underlying mechanisms remain incompletely understood. Here, we identify the adaptor protein SH2B3 as a critical driver of immune evasion in glioblastoma and show that elevated SH2B3 expression is associated with higher glioma grade and poorer survival in public datasets and clinical data. Although SH2B3 modulation did not significantly affect GBM cell proliferation, migration, or invasion <i>in vitro</i> assays, it significantly altered tumorigenesis <i>in vivo</i>, with overexpression enhancing and knockdown suppressing tumor growth, suggesting that microenvironmental factors may contribute to the <i>in vivo</i> phenotype. We further show that SH2B3 promotes immune evasion at least in part by upregulating PD-L1 expression. Mechanistically, SH2B3 facilitates BRCC3-dependent removal of K63-linked polyubiquitin chains from the m⁶A reader IGF2BP2, thereby stabilizing IGF2BP2 and preventing its autophagy-lysosome-dependent degradation. The stabilized IGF2BP2 then enhances the stability and translation of m⁶A-marked PD-L1 transcripts through m⁶A-dependent transcript recognition. Collectively, our findings reveal a novel SH2B3/BRCC3/IGF2BP2 axis connecting protein deubiquitination and RNA epigenetics to PD-L1-mediated immune evasion, highlighting SH2B3 as a promising therapeutic target for glioblastoma immunotherapy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"22 14","pages":"7557-7584"},"PeriodicalIF":11.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}