Biochimica et biophysica acta. Molecular basis of disease最新文献_第3页

ETV4 and ETV1-mediated downregulation of the secretory leukocyte protease inhibitor contributes to the indolent phenotype of early-stage prostate cancer ETV4和etv1介导的分泌性白细胞蛋白酶抑制剂的下调有助于早期前列腺癌的惰性表型。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-07 DOI: 10.1016/j.bbadis.2025.167975

Irene Cosi , Annalisa Moccia , Caterina Nannelli , Dario Rosini , Marta Iozzo , Michela Sica , Cristina Luceri , Rosario Notaro , Maria De Angioletti

{"title":"ETV4 and ETV1-mediated downregulation of the secretory leukocyte protease inhibitor contributes to the indolent phenotype of early-stage prostate cancer","authors":"Irene Cosi , Annalisa Moccia , Caterina Nannelli , Dario Rosini , Marta Iozzo , Michela Sica , Cristina Luceri , Rosario Notaro , Maria De Angioletti","doi":"10.1016/j.bbadis.2025.167975","DOIUrl":"10.1016/j.bbadis.2025.167975","url":null,"abstract":"<div><div>The Secretory Leukocyte Peptidase Inhibitor (SLPI) protects tissues from inflammation but it is overexpressed in various cancers. In prostate cancer (PC) SLPI exhibits a unique biphasic expression pattern: reduced levels in patients with early-stage disease and increased levels in those with advanced disease. Reduced SLPI levels, as in early-stage PC patients, were found in the prostate of a mouse model of early-stage PC, which overexpresses ETV4 into prostate. These reduced SLPI levels were modeled in normal human immortalized prostate RWPE cells by SLPI silencing that resulted, paradoxically, in increase of apoptosis and in decrease of cell migration, invasion, and epithelial-to-mesenchymal transition. Moreover, overexpression and silencing of the members of ETS PEA3-subfamily—ETV4 and ETV1—in human prostate cells (RWPE, PC3, LNCaP) showed that both genes mediate SLPI downregulation. Thus, the reduced levels of SLPI, resulting from ETV4- or ETV1-mediated downregulation, could curb the migratory, invasive, and anti-apoptotic capabilities of prostate cells partially counteracting ETV4 and ETV1 oncogenic effects, thereby contributing to the indolent phenotype of early-stage PC. Furthermore, in the androgen-competent LNCaP cells, androgens upregulate SLPI as well as ETV1, which in turn exerts a negative regulation on SLPI, resulting in a regulatory loop that modulates SLPI levels and explains the biphasic pattern of SLPI expression observed in PC patients. In conclusion, both reduced and increased SLPI levels appear to influence the biological and, possibly, the clinical phenotype of PC. These results uncover a relationship between genetic and microenvironment factors that together shape the evolution and progression of PC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167975"},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602458","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}

引用次数: 0

Nop2/Sun domain family member 5 contributes to tumorigenic properties in prostate cancer by engaging the PI3K-AKT pathway and tumor-associated macrophages Nop2/Sun结构域家族成员5通过参与PI3K-AKT通路和肿瘤相关巨噬细胞参与前列腺癌的致瘤性

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-07 DOI: 10.1016/j.bbadis.2025.167974

Mengjun Huang , Hailin Zou , Yufan Liang , Fei Cao , Qiliang Teng , Yupeng Guan , Yiting Wang , Jun Pang , Hanqi Lei

{"title":"Nop2/Sun domain family member 5 contributes to tumorigenic properties in prostate cancer by engaging the PI3K-AKT pathway and tumor-associated macrophages","authors":"Mengjun Huang , Hailin Zou , Yufan Liang , Fei Cao , Qiliang Teng , Yupeng Guan , Yiting Wang , Jun Pang , Hanqi Lei","doi":"10.1016/j.bbadis.2025.167974","DOIUrl":"10.1016/j.bbadis.2025.167974","url":null,"abstract":"<div><h3>Purpose</h3><div>Nop2/Sun domain family member 5 (NSUN5), a member of the m5C methylation family, plays a critical role in various biological processes by influencing RNA stability and regulating gene expression. The main purpose of this study was to determine the specific role of NSUN5 in prostate cancer (PCa) progression.</div></div><div><h3>Methods</h3><div>TCGA-PRAD database was used to analyze the differential expression of NSUN5 between PCa and normal tissues, as well as its association with survival outcomes, signaling pathways, and immune infiltration. Subsequently, immunohistochemistry was performed to evaluate NSUN5 expression in PCa tissues. Functional assays, including gain- and loss-of-function experiments, were conducted to explore the effects of NSUN5 on PCa cell proliferation, migration, and the expression of key proteins in relevant signaling pathways. Cell co-culture, in vivo experiments, and flow cytometry analysis were used to explore the effects of NSUN5 on macrophage polarization and the immune microenvironment of PCa.</div></div><div><h3>Results</h3><div>NSUN5 is significantly overexpressed in PCa tissues and is positively correlated with advanced disease stages and poor patient prognosis. Functionally, NSUN5 enhances in vitro proliferation and migration, as well as in vivo tumor growth, primarily through activation of the PI3K-AKT signaling pathway. Moreover, NSUN5 facilitates the polarization of macrophages into tumor-associated macrophages within PCa tissues, thereby contributing to immune evasion.</div></div><div><h3>Conclusion</h3><div>NSUN5 promotes PCa progression through the PI3K-AKT pathway and induces macrophage polarization toward a pro-tumor phenotype, promoting the formation of a suppressive tumor microenvironment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167974"},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588593","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}

引用次数: 0

Phosphodiesterase 12 facilitates the growth and metastatic capabilities of gastric cancer cells by activating the TCAF2/JAK2/STAT3 axis 磷酸二酯酶12通过激活TCAF2/JAK2/STAT3轴促进胃癌细胞的生长和转移能力

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-06 DOI: 10.1016/j.bbadis.2025.167973

Yi-Jin Liu, Huan-Xi Song, Jia-Hui Li, Xin-Ya Wang, Xiao-Fei Nie, Li-Na Zhang

{"title":"Phosphodiesterase 12 facilitates the growth and metastatic capabilities of gastric cancer cells by activating the TCAF2/JAK2/STAT3 axis","authors":"Yi-Jin Liu, Huan-Xi Song, Jia-Hui Li, Xin-Ya Wang, Xiao-Fei Nie, Li-Na Zhang","doi":"10.1016/j.bbadis.2025.167973","DOIUrl":"10.1016/j.bbadis.2025.167973","url":null,"abstract":"<div><div>Phosphodiesterase 12 (PDE12), also known as 2′-PDE, is a key molecule in the 2-5A antiviral system and a member of the endonuclease-exonuclease-phosphatase (EEP) superfamily of deadenylases. Current research on PDE12 mainly focuses on mitochondrial mRNA degradation, mitochondrial protein translation, and the related human diseases caused by mitochondrial oxidative phosphorylation disruption. However, the biological role and molecular mechanisms of PDE12 in human cancers remains unclear. In the present study, we found that PDE12 was highly expressed in gastric cancer tissues and gastric cancer cell lines. Gain- and loss-of-function experiments confirmed that PDE12 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of gastric cancer cells. PDE12 also promoted G1-S phase transition of gastric cancer cells by regulating the expression of G1 phase-specific Cyclin D1/CDK4 and Cyclin E/CDK2. Our further studies indicated that PDE12 positively regulated the expression of TRPM8 channel-associated factor 2 (TCAF2), which functioned as an oncogene in gastric cancer progression. TCAF2 knockdown significantly suppressed gastric cancer cell proliferation, migration and invasion, and reversed the promoting effect of PDE12 overexpression on gastric cancer cell growth and metastasis. Furthermore, our findings revealed a novel mechanism by which PDE12/TCAF2 axis promoted gastric cancer progression by activating the JAK2/STAT3 signaling pathway. Taken together, our data strongly indicate that PDE12 exerts an oncogenic function in gastric cancer progression at least partly via activating the TCAF2/JAK2/STAT3 signaling axis. These findings provide new insights into the tumorigenesis and metastasis of gastric cancer, and suggest that PDE12 may serve as a novel therapeutic target for gastric cancer.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167973"},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588594","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}

引用次数: 0

Anticancer and chemo-sensitizing effects of annonacin via p53-mediated DNA damage in ovarian cancer 番荔枝酸通过p53介导的卵巢癌DNA损伤的抗癌和化学增敏作用

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-04 DOI: 10.1016/j.bbadis.2025.167971

Yeying He , Jiaying Tong , Zijun Li , Lulu Yao , Chaoyue Chen , Li Wan , Wenyan Ma , Xiaohui Zheng , Namki Cho , Baoyou Huang

{"title":"Anticancer and chemo-sensitizing effects of annonacin via p53-mediated DNA damage in ovarian cancer","authors":"Yeying He , Jiaying Tong , Zijun Li , Lulu Yao , Chaoyue Chen , Li Wan , Wenyan Ma , Xiaohui Zheng , Namki Cho , Baoyou Huang","doi":"10.1016/j.bbadis.2025.167971","DOIUrl":"10.1016/j.bbadis.2025.167971","url":null,"abstract":"<div><div>Ovarian cancer (OC) is a highly lethal malignancy in women, often diagnosed at advanced stages. Carboplatin is the primary chemotherapy drug used clinically; however, most patients experience relapse and develop drug resistance after initial treatment, underscoring the urgent need for novel therapeutic strategies. This study investigated the anti-cancer activity and chemo-sensitizing effects of annonacin, an active compound in the fruit extract of <em>Asimina triloba</em>, as well as its underlying mechanisms in OC. Our results demonstrated that annonacin significantly inhibited OC cell viability, DNA replication, and proliferation, while inducing cell cycle arrest and senescence. Additionally, annonacin reduced OC cell-matrix adhesion and suppressed cell migration and invasion. Furthermore, annonacin enhanced the anti-OC efficacy of carboplatin by inducing substantial DNA damage, exhibiting a synergistic anticancer effect. Mechanistically, annonacin exerted potent anti-cancer and anti-migration activities through the p53 signaling pathway-mediated DNA damage response. When combined with carboplatin, this effect was further amplified. <em>In vivo</em> studies showed that annonacin effectively inhibited tumor growth in mice, and its combination with carboplatin demonstrated superior tumor-suppressive capabilities. Acute toxicity assays confirmed that annonacin possesses good biological safety <em>in vivo</em>. Collectively, these findings suggest that annonacin is a promising chemotherapeutic agent for OC treatment and highlight the potential of its combination with carboplatin to improve therapeutic outcomes in OC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167971"},"PeriodicalIF":4.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571202","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}

引用次数: 0

Advances in clinical studies of peptide drugs in stroke disease 脑卒中多肽药物的临床研究进展。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-03 DOI: 10.1016/j.bbadis.2025.167970

Yan Huo , Zhe Zhang , Suzhen Dong , Yijie Du , Mingliang Ma

{"title":"Advances in clinical studies of peptide drugs in stroke disease","authors":"Yan Huo , Zhe Zhang , Suzhen Dong , Yijie Du , Mingliang Ma","doi":"10.1016/j.bbadis.2025.167970","DOIUrl":"10.1016/j.bbadis.2025.167970","url":null,"abstract":"<div><div>Stroke remains a leading cause of death and disability globally, with limited treatment options currently available. Fortunately, peptide drugs have emerged as promising candidates for treating central nervous system disorders, including stroke. They offer high specificity, low toxicity, and efficient blood-brain barrier penetration, demonstrating significant therapeutic potential. This review systematically introduces several promising peptide drugs, analyzing their mechanisms, therapeutic efficacy in clinical trials, and potential applications. It also addresses critical challenges in peptide drug development for stroke therapy, such as optimizing dosing strategies, enhancing stability, and improving delivery systems. The analysis of current clinical evidence suggests that peptide-based therapeutics represent a promising frontier in stroke treatment, potentially offering new therapeutic options for patients. This comprehensive review not only highlights the current status of peptide drug development but also provides insights into future directions for advancing stroke therapy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167970"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565500","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}

引用次数: 0

Moderating role of fasting insulin on the levels of vitamin D in idiopathic central precocious puberty girls 空腹胰岛素对特发性中枢性性早熟女孩维生素D水平的调节作用

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-03 DOI: 10.1016/j.bbadis.2025.167966

Jun Sun , Ya Xiao , Shu-qin Jiang , Hong-ru Zhang , Wen-hui Shi , Jin-bo Li , Ying Yang , Wei Wang

{"title":"Moderating role of fasting insulin on the levels of vitamin D in idiopathic central precocious puberty girls","authors":"Jun Sun , Ya Xiao , Shu-qin Jiang , Hong-ru Zhang , Wen-hui Shi , Jin-bo Li , Ying Yang , Wei Wang","doi":"10.1016/j.bbadis.2025.167966","DOIUrl":"10.1016/j.bbadis.2025.167966","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D deficiency (VDD) is a risk factor for idiopathic central precocious puberty (ICPP), but the mechanism is unclear. The association between Vitamin D (Vit D) and insulin indicates that fasting insulin (FINS) may play a role in the influence of Vit D on the occurrence of ICPP.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the role of FINS in the impact of Vit D on ICPP risk in girls.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on 91 girls with ICPP and 47 girls with normal growth. Data on growth parameters, secondary sex characteristics, laboratory test results, and imaging results were collected. The moderating and mediating effects of FINS on the effect of Vit D on ICPP were analyzed.</div></div><div><h3>Results</h3><div>Girls with ICPP had higher FINS and homeostasis model assessment of insulin resistance (HOMA-IR) score and lower Vit D levels than those of controls. Among the girls with ICPP, those with VDD had significantly higher FINS and HOMA-IR values than those with Vit D insufficiency (VDI) or sufficiency (VDS). Moderation analysis revealed that FINS influenced the effect of Vit D on ICPP risk in girls with VDD. Receiver operating characteristic (ROC) curve analysis indicated that in the VDD group, the combination of 25(OH)D and FINS had an area under the ROC curve (AUC) of 0.910 for diagnosing ICPP.</div></div><div><h3>Conclusion</h3><div>FINS can moderate the effect of Vit D on ICPP in girls with VDD, and a combined assessment of FINS and Vit D may aid in the early diagnosis in these girls.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167966"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536226","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}

引用次数: 0

The DLX1-NCS1-MYC axis drives oncogenesis and progression in lung adenocarcinoma DLX1-NCS1-MYC轴驱动肺腺癌的发生和进展

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-03 DOI: 10.1016/j.bbadis.2025.167967

Bozhi Zhang , Hongyi Huang , Xun Zou , Xiuming Li , Jingliang He , Ningyang Xu , Bin Liu , Xiaozhu Shen , Wei Liu

{"title":"The DLX1-NCS1-MYC axis drives oncogenesis and progression in lung adenocarcinoma","authors":"Bozhi Zhang , Hongyi Huang , Xun Zou , Xiuming Li , Jingliang He , Ningyang Xu , Bin Liu , Xiaozhu Shen , Wei Liu","doi":"10.1016/j.bbadis.2025.167967","DOIUrl":"10.1016/j.bbadis.2025.167967","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related mortality globally, yet the transcriptional drivers of its progression are incompletely elucidated. Here, we identify DLX1, a novel homeobox transcription factor, as a pivotal oncogenic regulator in LUAD. Integrative transcriptomic analyses of RNA-sequencing and microarray datasets reveal significant overexpression of DLX1 in LUAD tissues compared to normal lung, a finding validated across independent datasets including The Cancer Genome Atlas (TCGA) and TIMER. Elevated DLX1 expression is associated with advanced clinical stages, TP53 mutations, and poor overall survival. Functional studies underscore the essential role of DLX1 in LUAD tumorigenesis. Silencing DLX1 impairs cell proliferation, invasion, and colony formation in vitro while significantly suppressing tumor growth in vivo. Mechanistically, transcriptomic profiling coupled with Gene Set Enrichment Analysis (GSEA) identifies DLX1 as a regulator of MYC-driven oncogenic pathways. Importantly, NCS1 is uncovered as a direct transcriptional target of DLX1. Chromatin immunoprecipitation (ChIP) and luciferase assays demonstrate that DLX1 binds two conserved motifs within the NCS1 promoter, driving its transcriptional activation. Functionally, NCS1 restores proliferative and invasive properties in DLX1-deficient LUAD cells, establishing its role as a mediator of DLX1-dependent oncogenicity. Furthermore, NCS1 itself acts as an upstream regulator of c-MYC and is significantly upregulated in LUAD, with its expression correlating with advanced stages, TP53 mutations, and unfavorable clinical outcomes. Collectively, our findings delineate the DLX1-NCS1-MYC axis as a critical transcriptional network underpinning LUAD progression.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167967"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549793","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}

引用次数: 0

ANXA1 facilitates myeloid-derived suppressor cell infiltration in the non-small cell lung cancer immunomicroenvironment via the STING/NF-κB/CXCL5/CXCR2 signaling axis to enhance tumor progression ANXA1通过STING/NF-κB/CXCL5/CXCR2信号轴促进非小细胞肺癌免疫微环境中髓源性抑制细胞浸润，促进肿瘤进展。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-03 DOI: 10.1016/j.bbadis.2025.167965

Xinyue Liu , Xiangtian Xiao , Yanqi Feng , Yiming Li , Shuxi Yao , Yuelin Han , Shu Xia

{"title":"ANXA1 facilitates myeloid-derived suppressor cell infiltration in the non-small cell lung cancer immunomicroenvironment via the STING/NF-κB/CXCL5/CXCR2 signaling axis to enhance tumor progression","authors":"Xinyue Liu , Xiangtian Xiao , Yanqi Feng , Yiming Li , Shuxi Yao , Yuelin Han , Shu Xia","doi":"10.1016/j.bbadis.2025.167965","DOIUrl":"10.1016/j.bbadis.2025.167965","url":null,"abstract":"<div><div>The infiltration of immune cells within the tumor microenvironment is a crucial determinant of the therapeutic efficacy of cancer immunotherapy. In non-small cell lung cancer (NSCLC), elucidating the regulatory mechanisms that govern the immune microenvironment is of substantial clinical importance. This study identifies Annexin A1 (ANXA1) as a key mediator in promoting the establishment of an immunosuppressive microenvironment driven by tumor cells. Clinical findings demonstrate that increased ANXA1 expression in NSCLC is highly correlated with worse prognosis and reduced effectiveness of immunotherapy. Complementary in vivo experiments further demonstrate that ANXA1 facilitates subcutaneous tumor progression and enhances the recruitment of myeloid-derived suppressor cells (MDSCs), thus fostering an immunosuppressive tumor microenvironment. Mechanistically, ANXA1 modulates the methylation status of UHRF1 (Ubiquitin-like plant homeodomain and RING finger domain-containing protein 1), disrupting DNA damage repair processes and leading to the accumulation of cytosolic double-stranded DNA (dsDNA), which triggers the activation of the STING/NF-κB/CXCL5 signaling axis. CXCL5 binds to its receptor CXCR2 on MDSCs, thereby promoting their recruitment. Importantly, inhibition of CXCR2 effectively reverses ANXA1-mediated MDSCs infiltration. These results elucidate the essential function of ANXA1 in modulating the recruitment of MDSCs within the immune environment of NSCLC, establishing ANXA1 as a significant therapeutic target for the advancement of innovative immunotherapeutic approaches.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167965"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568212","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}

引用次数: 0

GALNT4 controls aortic dissection by regulating vascular smooth muscle cell phenotype switch and dysfunction through the TGF-β/smad signaling GALNT4通过TGF-β/smad信号传导调节血管平滑肌细胞表型转换和功能障碍，从而控制主动脉夹层

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-07-02 DOI: 10.1016/j.bbadis.2025.167969

Liwei Guo , Pengcheng Wei , Lulu Zhou , Zhao Han , Xinru Wang , Duan Li

{"title":"GALNT4 controls aortic dissection by regulating vascular smooth muscle cell phenotype switch and dysfunction through the TGF-β/smad signaling","authors":"Liwei Guo , Pengcheng Wei , Lulu Zhou , Zhao Han , Xinru Wang , Duan Li","doi":"10.1016/j.bbadis.2025.167969","DOIUrl":"10.1016/j.bbadis.2025.167969","url":null,"abstract":"<div><div>Aortic dissection (AD) is a life-threatening vascular disorder whose underlying molecular mechanisms remain poorly understood. Polypeptide <em>N</em>-acetylgalactosaminyltransferase 4 (GALNT4), an enzyme that transfers <em>N</em>-acetylgalactosamine (GalNAc) to serine and threonine residues on target proteins, has been implicated in the development of cardiovascular diseases. However, its specific role in AD remains unclear. This study analyzed GALNT4 expression in human AD tissues and murine AD models induced by β-aminopropionitrile (BAPN) and angiotensin II (Ang II). Results revealed significantly elevated GALNT4 expression in the arteries of both human AD patients and AD mice (<em>P</em> < 0.01). Specifically, GALNT4 levels in vascular smooth muscle cells (VSMCs) from human and mouse AD arteries were markedly higher than in normal arteries. Smooth muscle cell (SMC)-specific knockdown of GALNT4 reduced AD incidence (53.8 % vs. 76.9 %) and rupture rates (28.6 % vs. 70.0 %), while improving AD pathology. This improvement was characterized by preserved contractile markers (α-SMA, SM22α) and suppressed synthetic markers (OPN, MMP2/9) in mice. In vitro, GALNT4 knockdown inhibited Ang II-induced phenotypic switching and migration of human aortic SMCs (29 % vs. 41 %, <em>P</em> < 0.01), whereas GALNT4 overexpression reversed these effects. Mechanistically, GALNT4 knockdown reduced O-GalNAcylation of TGF-βR2, inhibiting Smad2/3 phosphorylation and consequently blocking downstream Smad signaling pathway activation. In conclusion, GALNT4 regulates VSMC phenotypic switching and dysfunction through glycosylation-dependent activation of the TGF-β/Smad signaling pathway, positioning it as a potential therapeutic target for AD intervention.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167969"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556810","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}

引用次数: 0

Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases 细胞外囊泡在神经炎症和神经退行性疾病相互作用中的多方面作用

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-27 DOI: 10.1016/j.bbadis.2025.167960

Zhujie Deng, Haiyan Chen, Jiazhi Chen, Zhiyun Du, Wei Zhou, Zhengqiang Yuan

{"title":"Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases","authors":"Zhujie Deng, Haiyan Chen, Jiazhi Chen, Zhiyun Du, Wei Zhou, Zhengqiang Yuan","doi":"10.1016/j.bbadis.2025.167960","DOIUrl":"10.1016/j.bbadis.2025.167960","url":null,"abstract":"<div><div>Despite advances in understanding neurodegenerative disease mechanisms, effective treatments remain elusive. Extracellular vesicles (EVs), key mediators of intercellular communication within the central nervous system (CNS), are increasingly recognized for their involvement in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). In vivo studies demonstrate EVs' crucial role in maintaining CNS homeostasis, modulating neuroinflammatory responses, and influencing tissue repair and regeneration following injury, thereby impacting disease progression and recovery. Their unique properties, including small size and ability to cross the blood-brain barrier (BBB), position them as promising candidates for both biomarkers and therapeutics in CNS diseases. This review delves into the significant impact of neuroinflammation on neurodegenerative conditions, specifically focusing on the multifaceted contributions of EVs and their intricate interplay with the inflammatory landscape. We explore EV biogenesis, cargo composition, diverse roles in neuroinflammation (including intercellular communication and neuroprotection), their potential as biomarkers and drug delivery vehicles across the BBB for diagnosis or treatment of neuroinflammation implemented neurodegenerative diseases.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167960"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502586","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}

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