Biology Direct最新文献

{"title":"Autophagy is influenced by vitamin D₃ level in people with HIV-1.","authors":"Rita Casetti, Fabiola Ciccosanti, Harpreet Kaur Lamsira, Carmela Pinnetti, Valentina Mazzotta, Serena Ciolfi, Alessandra Sacchi, Alessandra Amendola, Giuseppe Ippolito, Mauro Piacentini, Roberta Nardacci","doi":"10.1186/s13062-025-00660-9","DOIUrl":"https://doi.org/10.1186/s13062-025-00660-9","url":null,"abstract":"<p><strong>Background: </strong>Autophagy is the primary catabolic process responsible for degrading intracellular components and potentially harmful cytosolic entities by delivering them to lysosomes. Notably, this mechanism is crucial for controlling intracellular pathogens, with significant implications for both innate and adaptive immunity. In the context of HIV-1 infection, emerging evidence suggests that autophagy contributes to immune responses against the virus. Various compounds can modulate autophagy, among which vitamin D₃ is particularly effective due to its ability to prevent inflammation and slow HIV-1 disease progression. Indeed, vitamin D₃ contributes to regulating both innate and adaptive immunity, thereby modulating antiviral and antibacterial inflammatory responses. Importantly, vitamin D₃ deficiency is highly prevalent among people with HIV (PWH) and has been associated with an increased risk of severe disease progression.</p><p><strong>Results: </strong>In this study, we investigated the relationship between serum vitamin D₃ levels and the expression of autophagy markers in peripheral blood mononuclear cells from different categories of PWH: PWH under antiretroviral therapy (ART) with either normal vitamin D₃ levels or hypovitaminosis, and treatment-naïve PWH with either normal vitamin D₃ levels or hypovitaminosis. Our results show that low vitamin D₃ blood levels is associated with lower expression of the main factors involved in the autophagy mechanism, particularly in treatment-naïve PWH.</p><p><strong>Conclusions: </strong>Our findings suggest that normal blood level of vitamin D₃ may play a crucial role in promoting autophagy in PWH. The observed differences in autophagy-related protein expression between ART-treated and untreated individuals underscore the intricate relationship between vitamin D₃ levels, ART exposure, and autophagic regulation. This is a preliminary exploration of the effects of vitamin D₃ on autophagy in PWH. Further studies are needed to deepen and explore the interplay between vitamin D₃ and autophagy in greater depth. A better understanding of these mechanisms could help to develop novel therapeutic strategies aimed at mitigating immune depletion and chronic inflammation, ultimately improving clinical outcomes for individuals living with HIV.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293350","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":"Estrogen receptor alpha dynamics and plasticity during endocrine resistance.","authors":"Aswathy Sivasailam, Kiran S Kumar, Aparna Geetha Jayaprasad, Shine Varghese Jancy, Ashwathi Harikumar, P S Unnikrishnan, K C Sivakumar, P J Jain Tiffee, Aman Munirpasha Halikar, S S Nithin, Prakash R Pillai, Shivanshu Kumar Tiwari, Vishnu S Sanjeev, A V Surabhi, T R Santhoshkumar","doi":"10.1186/s13062-025-00653-8","DOIUrl":"https://doi.org/10.1186/s13062-025-00653-8","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is subdivided into four distinct subtypes based on the status of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) as HER2^-/HR⁺, HER2⁺/HR⁺, HER2⁺/HR^- and HER2^-/HR^-. Among this, ERα positive breast cancer, even though they respond to endocrine treatment, half of the patients acquire resistance and progress with metastasis despite ERα status. Spatio-temporal changes in ERα and their loss under treatment pressure have been reported in a subset of patients, which is a serious problem.</p><p><strong>Results: </strong>We have demonstrated that in vitro-generated resistance is correlated with the down regulation of ERα. To study the ERα status transition in live cells, triple-negative breast cancer cells were engineered to express EGFP-ERα, which further supported the existence of complex intracellular signaling that regulates ERα plasticity even in unperturbed conditions. Single-cell clones generate heterogeneity and loss of expression depending on proliferative cues. However, the initial response of cells to 4 μM of 4-hydroxytamoxifen and 1 μM of endoxifen involves up-regulation of ERα, likely due to its early effect on the proteasome or autophagy pathway. Supporting this, inhibition of autophagy and the proteasome further enhanced the expression of ERα. Systematic analysis of RNA sequencing of ERα stable cells further confirmed that ERα regulates diverse intracellular signaling networks such as ubiquitin, proteasome pathways, cell proliferation and Unfolded Protein Responses (UPR), implicating its direct role in post-translational protein modifications. Cell cycle indicator probe expressing receptor-positive breast cancer cells confirmed the ERα expression heterogeneity both in 2D and 3D culture in a cell cycle phase-independent manner.</p><p><strong>Conclusions: </strong>Overall, the study confirms the cell's intrinsic post-transcriptional mechanisms of ERα plasticity that could play a role in receptor heterogeneity and tumor progression under endocrine treatment, which warrants further investigation.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"70"},"PeriodicalIF":5.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293351","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":"A multi-omics exploration of PPARG activation in colon cancer: kinases featuring a PPRE sequence within regulatory regions.","authors":"Pritha Saha, Palaniyandi Ravanan, Priti Talwar","doi":"10.1186/s13062-025-00654-7","DOIUrl":"10.1186/s13062-025-00654-7","url":null,"abstract":"<p><strong>Background: </strong>As members of the nuclear receptor (NR) family of transcription factors, peroxisome proliferator-activated receptors (PPARs) regulate essential cellular processes, including lipid metabolism, glucose uptake, cell proliferation, and programmed cell death through ligand-mediated activation. Within the PPAR subfamilies, PPAR-γ (PPARG) is crucial to the development of fat cells, sensitivity to insulin, apoptosis, and metastasis. Furthermore, it demonstrates properties that counteract fibrosis and inflammation, thus establishing itself as a notable target for therapeutic interventions against conditions such as type 2 diabetes and cancer. PPARG is reported to be a promising target for patients diagnosed with colorectal cancer (CRC). Globally, colorectal cancer ranks as the third most prevalent malignancy and is responsible for approximately 10% of all cancer mortalities, and PPARG is significantly expressed in 70% of the sporadic CRC. In individuals with CRC, the precise function of PPARG remains not entirely comprehended and elucidation of the PPARG transcriptional regulation in CRC seems promising.</p><p><strong>Results: </strong> This study integrates RNA-seq and ChIP-seq reads to analyze the effects of Rosiglitazone on HT-29 colon cancer cells. Peak calling analysis from ChIP-seq data identified 14,000 to 34,000 binding sites for PPARG across different experimental conditions. RNA-seq analysis highlighted significant differential gene expression in Rosiglitazone-treated cells, with 4362 and 6780 genes significantly regulated at 24 and 48 h, respectively. The correlation of these datasets with PPRE-associated kinases resulted in the identification of 18 differentially expressed genes (DEGs), followed by subsequent analysis of gene ontology, pathway enrichment, and protein-protein interactions, culminating in the elucidation of seven hub genes (PTK2, HGS, CDK8, PRPF6, PRKDC, PRKCZ, MET). Further these hub genes correlated with CRC progression and patient survival. Validation using independent GEO datasets (GSE113513 and GSE210693) and gene effect scores derived from CRISPR knockout screens further supported the functional impact of these hub genes. Disease ontology and mutational analyses implicated the hub genes in various cancers, including CRC. Moreover, miRNA analysis identified 37 experimentally validated miRNAs potentially modulating hub gene expression.</p><p><strong>Conclusions: </strong>These findings advance our understanding of PPARG's regulatory network and underscore its potential as a therapeutic target, establishing a robust framework for future research in PPARG-related pathways.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"68"},"PeriodicalIF":5.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274170","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":"Affibodies as valuable tool to prevent β₂m aggregation under lysosomal-like conditions.","authors":"Visentin Cristina, Rizzi Giulia, Wen Yin, Hotot Mathilde, Roy Dipambita, Gräslund Torbjörn, Capelli Riccardo, Ricagno Stefano","doi":"10.1186/s13062-025-00659-2","DOIUrl":"10.1186/s13062-025-00659-2","url":null,"abstract":"<p><p>Beta-2 microglobulin (β₂m) is a small protein that forms the invariant subunit of the Major Histocompatibility Complex I. Monomeric β₂m is stable under physiological conditions, however high local concentrations can induce misfolding, leading to amyloid deposition. This accumulation has been recently observed in the lysosomes of tumour-associated macrophages from patients affected by multiple myeloma. Such aggregation has been linked to inflammation and tumour progression. Stabilizing the native state of β₂m could be the first step towards preventing this cancer-promoting process. To achieve this goal, the effect of affibody molecules, small and stress-resistant affinity proteins, was tested. Three affibodies molecules were selected against β₂m. Affibody-β₂m complex formation was initially assessed by size exclusion chromatography and subsequently confirmed by microscale thermophoresis and isothermal titration calorimetry. In parallel, in presence of one of the affibody (Z_{β2m_01}) a significant reduction in β₂m aggregation was observed. The inhibition of amyloid formation was also confirmed by transmission electron microscopy. Taken together, these results indicate that Z_{β2m_01} has the potential to act as β₂m aggregation inhibitor under lysosomal-like pH values.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"67"},"PeriodicalIF":5.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246437","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":"scE2EGAE: enhancing single-cell RNA-Seq data analysis through an end-to-end cell-graph-learnable graph autoencoder with differentiable edge sampling.","authors":"Shuo Wang, Yuanning Liu, Hao Zhang, Zhen Liu","doi":"10.1186/s13062-025-00616-z","DOIUrl":"10.1186/s13062-025-00616-z","url":null,"abstract":"<p><strong>Background: </strong>Single-cell RNA sequencing (scRNA-Seq) technology reveals biological processes and molecular-level genomic information among individual cells. Numerous computational methods, including methods based on graph neural networks (GNNs), have been developed to enhance scRNA-Seq data analysis. However, existing GNNs-based methods usually construct fixed graphs by applying the k-nearest neighbors algorithm, which may result in information loss.</p><p><strong>Methods: </strong>To address this problem, we propose scE2EGAE, which learns cell graphs during the training processes. Firstly, the scRNA-Seq data is fed into a deep count autoencoder (DCA). Secondly, the hidden representations of DCA are extracted and then used to generate cell-to-cell graph edges through a straight-through estimator (STE) based on top-k sampling and Gumbel-Softmax. Finally, the generated cell-to-cell graph and scRNA-Seq data are fed into the GNNs-based downstream tasks. In this paper, we design a graph autoencoder which performs denoising on scRNA-Seq data as the downstream task.</p><p><strong>Results: </strong>We evaluate scE2EGAE on eight public scRNA-Seq datasets and compare its performance with seven existing scRNA-Seq data denoising methods. In this paper, extensive experiments are conducted, encompassing: 1) the evaluation of denoising performance, with metrics including mean absolute error, Pearson correlation coefficient, and cosine similarity; 2) the assessment of clustering performance of the denoised results, utilizing adjusted rand index, normalized mutual information and silhouette score; and 3) the evaluation of the cell trajectory inference performance of the denoised results, measured by the pseudo-temporal ordering score. The results show that, on the scRNA-Seq data denoising task, scE2EGAE outperforms most of the methods, proving that it can learn cell-to-cell graphs containing real information of cell-to-cell relationships.</p><p><strong>Conclusions: </strong>In this paper, we validate the proposed scE2EGAE method through its application to the denoising task of scRNA-Seq data. This method demonstrates its capability to learn inter-cellular relationships and construct cell-to-cell graphs, thereby enhancing the downstream analysis of scRNA-Seq data. Our approach can serve as an inspiration for future research on scRNA-Seq analysis methods based on GNNs, holding broad application prospects.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"66"},"PeriodicalIF":5.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156526","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":"Macrophage Notch1 drives septic cardiac dysfunction by impairing mitophagy and promoting NLRP3 activation.","authors":"Yanjun Zheng, Jingrong Lin, Guoqing Wan, Xuefeng Gu, Jian Ma","doi":"10.1186/s13062-025-00657-4","DOIUrl":"10.1186/s13062-025-00657-4","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening condition with limited therapeutic options, characterized as excessive systemic inflammation and multiple organ failure. Macrophages play critical roles in sepsis pathogenesis. Although numerous studies support the critical role of Notch signaling in most inflammatory diseases, the function of Notch1 signaling in macrophages activation and its underlying molecular mechanism during sepsis has not been fully elucidated.</p><p><strong>Methods: </strong>We evaluated Notch1 expression in a lipopolysaccharide (LPS)-induced model of septic cardiac dysfunction. Using macrophage-specific Notch1 knockout mice (NOTCH1^ΔMyelo) in conjunction with AAV-F4/80-mediated NICD1 overexpression, we investigated the impact of Notch1 on septic cardiac injury. LPS-stimulated bone marrow-derived macrophages (BMDMs) were analyzed by flow cytometry and ELISA to assess mitochondrial damage and inflammasome activation. Mitophagy flux and related protein levels were quantified, and a mitophagy inhibitor was applied to further delineate Notch1's in vivo role. Downstream targets of Notch1 were identified and validated via ChIP-qPCR and luciferase reporter assays.</p><p><strong>Results: </strong>Intraperitoneal injection of LPS markedly impaired cardiac function, increased macrophage infiltration, and elevated Notch1 expression compared with PBS-treated controls. Notch1 expression was inversely correlated with cardiac performance in LPS-treated mice. Notably, macrophage-specific deletion of Notch1 significantly improved cardiac function, whereas NICD1 overexpression worsened LPS-induced cardiac injury. NOTCH1^ΔMyelo macrophages showed reduced mitochondrial damage and diminished activation of NLRP3-dependent caspase-1. Moreover, LPS induced mitophagy, an effect that was further enhanced by Notch1 knockout. Mechanistically, ChIP-seq and qPCR analyses revealed that NICD1 upregulates Mst1 transcription. Furthermore, overexpression of Mst1 counteracted the increased mitophagy in Notch1-deficient macrophages, resulting in elevated mitochondrial reactive oxygen species production, inflammatory cytokine secretion, and caspase-1 activation during prolonged LPS stimulation.</p><p><strong>Conclusion: </strong>Our study uncovers a novel role for Notch1 in exacerbating LPS-induced septic cardiac dysfunction by suppressing mitophagy in macrophages. These findings suggest that targeting Notch1 may offer a promising therapeutic strategy to mitigate sepsis-induced inflammation by restoring proper mitophagy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"65"},"PeriodicalIF":5.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141544","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":"LDHA-mediated YAP lactylation promotes the tumor progression of hepatocellular carcinoma by inducing YAP dephosphorylation and activation.","authors":"Xiaoyong Wei, Long Zou, Yanqing Huang, Chuan Qiu, Guang Cheng, Ye Chen, Jun Rao","doi":"10.1186/s13062-025-00655-6","DOIUrl":"10.1186/s13062-025-00655-6","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is among the deadliest cancers globally. Yes-Associated Protein (YAP), a Hippo pathway effector, crucially regulates cell proliferation and apoptosis. Recent research has implicated YAP's role in HCC progression, but the mechanisms are unclear. This study aims to clarify YAP's function in HCC, emphasizing its regulation of key pathways and targets.</p><p><strong>Results: </strong>Gene knockout and overexpression models were established in nude mice and cell lines of HCC cells to investigate YAP's impact on tumorigenesis. Additionally, functional assays and molecular biology techniques were employed to identify YAP's regulatory networks. The study demonstrates that LDHA-regulated lactate production promotes YAP activation and malignant phenotypes in HCC. Overexpression of LDHA in HepG2 and Huh7 cells increased lactate levels and activated the YAP pathway, enhancing cell proliferation, migration, and invasion. Lactate treatment also promoted these malignant phenotypes by inhibiting YAP phosphorylation at Ser127. In a xenograft model, lactate accelerated tumor growth through YAP activation. YAP lactylation at K102 antagonized its Ser127 phosphorylation, further promoting malignant progression.</p><p><strong>Conclusions: </strong>This study highlights the significance of YAP in HCC pathogenesis, providing insights into potential therapeutic targets for HCC management.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"64"},"PeriodicalIF":5.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141541","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":"Allosteric modulation of Grb2 drives ligand-dependent signal responses.","authors":"Mariana Di Felice, Lucrezia Romana Rolfi, Julian Toso, Valeria Pennacchietti, Eduarda S Ventura, Angelo Toto, Antonella Tramutola, Stefano Gianni","doi":"10.1186/s13062-025-00656-5","DOIUrl":"10.1186/s13062-025-00656-5","url":null,"abstract":"<p><p>Adaptor proteins play a crucial role in signal transduction by facilitating the assembly of protein complexes at specific subcellular domains. These multifunctional molecules contain multiple binding modules that enhance the efficiency and flexibility of cellular signaling pathways, thereby orchestrating complex responses. Among these proteins, Grb2 (growth factor receptor-bound protein 2) emerges as a key regulator owing to its unique \"sandwich\" structure. Despite lacking intrinsic enzymatic activity, recent investigations have revealed that Grb2 acts not merely as a passive bridge but also utilizes intramolecular allosteric communication to modulate binding specificity. In this study, we compared the kinetic binding properties of SH2-SH3 belonging to Grb2 with Gab2 and the same experiment with bound states of the SH2 domain using two different peptides that mimics the physiological ligands of SH2. Our results demonstrate that the SH2 domain plays a critical regulatory role, exhibiting remarkably distinct behaviors in free and bound states, and depending on the ligand it binds to. This suggests how selectivity can be modulated by intradomain allostery. In vitro functional assays measuring the activation levels of the target protein further supported our hypothesis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"63"},"PeriodicalIF":5.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131852","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":"Early-stage administration of hydroxytyrosol extends lifespan and delays aging in C. elegans.","authors":"Nannan Du, Lishuo Song, Ruigang Yang, Kexin Liu, Zubiao Niu, Zhanfeng Zhang, Qiang Sun","doi":"10.1186/s13062-025-00634-x","DOIUrl":"10.1186/s13062-025-00634-x","url":null,"abstract":"<p><strong>Background: </strong>This study employs Caenorhabditis elegans (C. elegans) as a model organism to explore the anti-aging effects of hydroxytyrosol (HT) and its underlying mechanisms.</p><p><strong>Results: </strong>The findings reveal that HT significantly extends the lifespan of C. elegans while improving their functional performance (motility and pharyngeal function), and antioxidant capacity when administered on the first day of adulthood (D1). However, its efficacy diminishes when treatment begins on or after the third day of adulthood (D3). HT prolongs lifespan through a mechanism akin to that of skn-1 modulating the oxidative stress pathway.</p><p><strong>Conclusions: </strong>This study suggests that the administration timing is an important factor for of anti-oxidation compounds to be effective in counteracting aging.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"62"},"PeriodicalIF":5.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118878","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":"Mechanism of LINC01018/miR-182-5p/Rab27B in the immune escape through PD-L1-mediated CD8⁺ T cell suppression in glioma.","authors":"Su Hu, Guoshuo Chen, Aiping Luo, Hailin Zhao, Dan Li, Biao Peng, Jike Du, Dongdong Luo","doi":"10.1186/s13062-025-00651-w","DOIUrl":"10.1186/s13062-025-00651-w","url":null,"abstract":"<p><strong>Background: </strong>Glioma is a malignant tumor associated with poorer prognosis. This study aims to elucidate the mechanism of LINC01018/miR-182-5p/Rab27B axis in PD-L1-mediated CD8⁺ T cell suppression in the progression of gliomas.</p><p><strong>Methods: </strong>LINC01018, miR-182-5p, and Rab27B expression levels in glioblastoma tissues were measured. The proportion of infiltrating macrophages and monocytes and CD8⁺ T cell function were assessed. The relationship between miR-182-5p and Rab27B was analyzed. Glioma cell activity, invasion, and migration were measured. The expression of E-cadherin, N-cadherin, Vimentin, PD-L1, iNOS, and CD206 was determined. Glioma cell-derived EVs were isolated, and the co-localization of Rab27B and PD-L1 and the binding of Rab27B to PD-L1 were analyzed. The endocytosis of EVs by microglia was assayed. The impact of LINC01018/miR-182-5p/Rab27B on glioma growth was observed. The function of macrophages and CD8⁺ T cells in tumors was analyzed.</p><p><strong>Results: </strong>Rab27B was downregulated, and infiltrating macrophages and monocytes were increased in glioblastoma. miR-182-5p inhibited Rab27B expression. Rab27B knockdown reverses the inhibitory effect of LINC01018 overexpression on glioma cell growth. Glioma cells-derived EVs with low Rab27B expression carried more PD-L1 to increase PD-L1 expression and M2 polarization in microglia. LINC01018 overexpression reduced macrophages in orthotopic tumors. CD8⁺ T cell numbers showed no significant difference, but TIM-3 increased and IFN-γ decreased. miR-182-5p inhibition enhanced the therapeutic effect of anti-PD-L1, which was reversed after glioma cell-derived EVs.</p><p><strong>Conclusion: </strong>LINC01018 promotes PD-L1-mediated CD8⁺ T cell suppression via the miR-182-5p/Rab27B axis in glioma cell-derived EVs, thereby contributing to immune escape in gliomas.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"61"},"PeriodicalIF":5.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118833","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}