Biochemical and biophysical research communications最新文献

{"title":"Twisting and untwisting of actin and tropomyosin filaments may be involved in the molecular mechanism of muscle contraction","authors":"Yurii S. Borovikov ,&nbsp;Maria V. Tishkova ,&nbsp;Olga E. Karpicheva","doi":"10.1016/j.bbrc.2025.152080","DOIUrl":"10.1016/j.bbrc.2025.152080","url":null,"abstract":"<div><div>Polarized fluorescence microscopy in “ghost” muscle fibers containing F-actin, tropomyosin, and myosin heads labeled with FITC-phalloidin, 5-IAF, and 1,5-IAEDANS probes, respectively, provided new insights into the molecular mechanisms of muscle contraction. Simulation of different stages of muscle contraction revealed significant changes in probe orientation and mobility, as well as variations in the bending stiffness of actin and tropomyosin filaments. Fluorescence analysis showed that in the AM∗•ATP state, myosin heads deviate from the axis of actin and weakly interact with thin filaments. Actin filaments exhibit excessive twisting, while tropomyosin filaments untwist. This is accompanied by a 115 % increase in actin filament stiffness and a 32 % increase in tropomyosin filament stiffness. The transition to the AM•ADP state aligns the myosin heads and induces actin untwisting. The release of inorganic phosphate reduces actin stiffness by 45 % and increases tropomyosin stiffness by 9 %. We propose that the untwisting of supertwisted actin filaments, combined with myosin head tilting towards actin and increased tropomyosin twist and stiffness, causes thin filaments to slide along thick filaments. The synchronized sliding of thin filaments relative to thick filaments ultimately generates the mechanical force that drives muscle contraction.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152080"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of indirect pathways enhancing the biocompatibility of DOX/GO/Fe3O4 nanomaterials in Glioblastoma: Gene network modeling and pathway analysis","authors":"Amin Alvani ,&nbsp;Negar Mottaghi-Dastjerdi ,&nbsp;Ahmad Gholami ,&nbsp;Abozar Ghorbani ,&nbsp;Zeinab Pazhoohesh ,&nbsp;Mohammad Pajdam ,&nbsp;Ali Eskanderi ,&nbsp;Mohammad-Javad Niazi","doi":"10.1016/j.bbrc.2025.152077","DOIUrl":"10.1016/j.bbrc.2025.152077","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Conventional treatment includes maximal safe surgical resection combined with radiotherapy and chemotherapy.</div></div><div><h3>Materials and methods</h3><div>This study analyzed gene networks to identify key gene clusters and hub genes involved in apoptosis using Cytoscape in Glioblastoma cell line samples treated with GO/Fe₃O₄ and DOX/GO/Fe₃O₄ for 24 h. The cytotoxicity of DOX on A-172 cells was assessed using the MTT assay. Real-time PCR was used to evaluate the expression of Casp3, Bcl-2, and BAX genes in A-172 cells treated with free DOX and DOX-loaded GO/Fe₃O₄ (DOX/GO/Fe₃O₄).</div></div><div><h3>Result</h3><div>the IC50 values for free DOX and DOX/GO/Fe₃O₄ were determined to be 80 μg/mL and 40 μg/mL, respectively. Real-time PCR analysis revealed that both DOX/GO/Fe₃O₄ and free DOX upregulated the expression of Casp3 and Bax genes, with minimal changes observed in Bcl-2 expression in A-172 cells. Bioinformatic analysis using NetworkAnalyst's \"Mapping Overview\" indicated that miR-92a-2-5p is a potential therapeutic target for preventing myocardial damage and enhancing the biocompatibility of DOX/GO/Fe₃O₄ in GBM. Furthermore, conditions of cancer cells showed similarities to embryonic cells, with involvement in thermogenesis (miR-143), absorption by vascular endothelial cells, increased angiogenesis (miR-135ab/135a-5p), axon regeneration (miR-7/7 ab), and regulation of circadian rhythm, aging, oxidative stress, mitochondrial dysfunction, and neuroinflammation.</div></div><div><h3>Conclusion</h3><div>Bioinformatic analysis suggests that autophagy-regulating nanomaterials and their incorporation into nano-complexes can enhance the biocompatibility of DOX/GO/Fe₃O₄. The nanocomplex's pH sensitivity prolongs drug exposure in GBM, and targeting GBM with an external magnetic field presents a promising approach for GBM treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152077"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural basis for substrate selectivity and evolutionary insights into human choline phosphotransferase 1","authors":"Yonglin He,&nbsp;Yufan Yang,&nbsp;Meng Yang,&nbsp;Hongwu Qian","doi":"10.1016/j.bbrc.2025.152082","DOIUrl":"10.1016/j.bbrc.2025.152082","url":null,"abstract":"<div><div>Phosphatidylcholine (PC) and phosphatidylethanolamine (PE), the core phospholipids maintaining eukaryotic membrane structure and function, are predominantly synthesized through the Kennedy pathway. The final step of this pathway is catalyzed by choline phosphotransferase 1 (CHPT1) and choline ethanolamine phosphotransferase 1 (CEPT1). Notably, although these enzymes show high sequence homology, CHPT1 specifically synthesizes PC while CEPT1 catalyzes both PC and PE production, and the mechanism of this substrate selectivity remains unclear. Here, we report the 3.7 Å cryo-EM structure of human CHPT1 (hCHPT1), revealing a homodimer in which each monomer consists of an N-terminal domain, a catalytic domain, and a dimerization domain. Through structural and sequence analyses, along with biochemical characterizations, we identified important residues in the catalytic domain that regulate substrate selectivity. Moreover, cross-species sequence alignment showed ovipara CHPT1 conserves important substrate selectivity residues with CEPT1. This residues conservation may endow ovipara CHPT1 with catalytic bifunctionality comparable to CEPT1. These findings not only elucidate the structural basis for substrate selectivity between CHPT1 and CEPT1, but also provide novel evolutionary perspectives on phospholipid synthase adaptation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152082"},"PeriodicalIF":2.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FuHsi maintains nucleolar integrity","authors":"Xiaohui Yang ,&nbsp;Ziyue Jiang ,&nbsp;Songzhe Wu ,&nbsp;Shan Gao","doi":"10.1016/j.bbrc.2025.152083","DOIUrl":"10.1016/j.bbrc.2025.152083","url":null,"abstract":"<div><div>The nucleolus is a dynamic, membrane-less organelle that assembles around ribosomal DNA (rDNA) repeats and governs ribosome biogenesis. Its structural organization is tightly linked to its function. In our previous work, we identified FuHsi as a novel rDNA transcriptional regulator. However, its role in nucleolar architecture remains unknown. Here, we show that FuHsi co-localizes with UBF, RPA194, TCOF1, and rDNA, and is encapsulated by FBL and NPM1. Knockdown of FuHsi leads to the coordinated loss of these components from the nucleolus and uniquely causes rDNA to disperse into the nucleoplasm—a phenotype not observed upon TCOF1 depletion. Notably, TCOF1 knockdown displaces UBF but not FuHsi and rDNA, while UBF or RPA194 knockdown leads to peripheral redistribution of FuHsi. These data suggest that FuHsi functions upstream of TCOF1 and UBF and is required for anchoring rDNA at the nucleolar core. We propose that FuHsi functions at the top of the nucleolar assembly cascade and identifies a novel initiation step critical for rDNA organization and nucleolar formation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152083"},"PeriodicalIF":2.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening ligands interacting with NDUFS3 from Oroxylum indicum extract using bioaffinity ultrafiltration combined with in vitro protein purification","authors":"Ya-fei Ma ,&nbsp;Xiao-xue Zhang ,&nbsp;De-zhi Kong ,&nbsp;De-qiang Li","doi":"10.1016/j.bbrc.2025.152078","DOIUrl":"10.1016/j.bbrc.2025.152078","url":null,"abstract":"<div><div><em>Oroxylum indicum</em> (<em>O. indicum</em>) is a common traditional Chinese medicine, but its neuroprotective effects in Parkinson's disease (PD) model have not been fully elaborated. Mitochondrial complex I dysfunction is the core pathology of oxidative stress injury in PD, and the mechanism of regulating the activity of its key subunit NADH: Ubiquinone Oxidoreductase Core Subunit S3 (NDUFS3) has not been clarified. To explore the potential therapeutic effects of <em>O</em>. <em>indicum</em> on PD and reveal the potential active compounds and molecular mechanism of action behind the treatment of PD by <em>O indicum</em> extract (OIE), in the present study, the mitochondrial complex I subunit NDUFS3 was selected as the PD disease target, and a “three-in-one” system combing target purification of NDUFS3 protein, affinity ultrafiltration screening and validation-analysis of molecular mechanism was constructed. Results suggest that the active compounds in <em>O indicum</em> screened by affinity screening can target and regulate the expression of NDUFS3, lower the mitochondrial membrane potential, reduce oxidative stress, and increase the ATP content, thus exerting anti-PD effects at the cellular and animal levels. The integrated approach of protein purification, affinity ultrafiltration screening and pharmacological validation is pivotal for efficiently identifying active compounds and uncovering their mechanisms in anti-PD research, thereby proving a reference for drug discovery of neurodegenerative diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152078"},"PeriodicalIF":2.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure and inhibition mechanism of AcrIIA11","authors":"Xueli Cao ,&nbsp;Zirui Gao ,&nbsp;Peipei Yin ,&nbsp;Hao Wang ,&nbsp;Lingguang Yang","doi":"10.1016/j.bbrc.2025.152073","DOIUrl":"10.1016/j.bbrc.2025.152073","url":null,"abstract":"<div><div>Anti-CRISPR (Acr) proteins are naturally evolved inhibitors that precisely target and suppress CRISPR-Cas systems, representing a sophisticated molecular arms race between bacteriophages and their bacterial hosts. While Class 1 systems dominate among sequenced prokaryotic genomes, Class 2 systems remain primary sources of editing tools. Here, we report the structural and mechanistic characterization of AcrIIA11, an anti-CRISPR protein that simultaneously inhibits <em>Streptococcus pyogenes</em> (SpyCas9) and <em>Staphylococcus aureus</em> Cas9 (SauCas9). The 3.2 Å crystal structure reveals a compact α/β fold with distinct electropositive clefts implicated in DNA binding. While DALI analysis identified structural homology to transcriptional regulators and the RecA inhibitor PsiB (RMSD 3.3 Å), functional studies established that AcrIIA11 forms stable ternary complexes with both Cas9 orthologs and sgRNA. Biochemical assays demonstrated stronger inhibition of SauCas9 compared to SpyCas9, with EMSA revealing a critical dichotomy: AcrIIA11 maintains SauCas9-sgRNA binding to specific target DNA while completely blocking cleavage activity. Computational docking localizes AcrIIA11 at the HNH-RuvC interface without obstructing DNA-binding channels in SauCas9, suggesting allosteric inhibition through HNH domain displacement. This work establishes AcrIIA11 as a dual-purpose Cas9 inhibitor that preserves target recognition while inactivating nuclease function—a mechanism with potential applications in precision CRISPR control.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"772 ","pages":"Article 152073"},"PeriodicalIF":2.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pexidartinib impairs liver mitochondrial functions causing cell death in primary human hepatocytes at clinically relevant concentrations","authors":"Qiang Shi ,&nbsp;Lijun Ren ,&nbsp;Katy Papineau ,&nbsp;Xi Yang ,&nbsp;Li Pang ,&nbsp;Jessica Hawes Oliphant ,&nbsp;Laura Schnackenberg ,&nbsp;William Mattes","doi":"10.1016/j.bbrc.2025.152075","DOIUrl":"10.1016/j.bbrc.2025.152075","url":null,"abstract":"<div><div>Pexidartinib is a regulatory agency approved small molecule kinase inhibitor (KI) with a boxed warning for hepatotoxicity, and FDA requires a Risk Evaluation and Mitigation Strategy (REMS) to mitigate such risk. The mechanism of pexidartinib hepatotoxicity is poorly understood. As mitochondrial injury and hepatocyte toxicity have been proposed to be a shared mechanism for the hepatotoxicity induced by many KIs, here we examined pexidartinib for such liabilities. Freshly isolated rat liver mitochondria, submitochondrial fractions, and cryopreserved primary human hepatocytes (PHHs) – the gold standard in vitro model for drug hepatotoxicity – were treated with pexidartinib at clinically relevant concentrations, and mitochondrial functions and cytotoxicity were assessed. In isolated mitochondria, the state 3 oxygen consumption rates of glutamate/malate- and succinate-driven respiration were both decreased by pexidartinib, while the state 4 oxygen consumption rates were unaffected. In submitochondrial fractions, the activities of respiratory chain complex (RCC) I and V, but not II, III, IV, were significantly inhibited by pexidartinib. In PHHs, as measured by a Seahorse system, pexidartinib decreased basal, spare, maximal, and adenosine triphosphate (ATP)-linked respirations at 2 h in the absence of cell death. Pexidartinib also inhibited cellular ATP level, increased reactive oxygen species, and caused cell death after 24 h. However, activities of caspases were unaffected. Importantly, the detrimental effects noted above occurred at pexidartinib concentrations of 0.5- to 2.5-fold of the human peak blood concentration (C_max) achieved with the recommended therapeutic dose. These data suggest that mitochondrial injury and hepatocyte toxicity are involved in the mechanism of pexidartinib-induced hepatotoxicity.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152075"},"PeriodicalIF":2.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of lysine-acetylated proteins in the anti-inflammatory effects of luteolin-gadolinium on macrophages","authors":"Hongjia Zhang ,&nbsp;Huhu Tian ,&nbsp;Yanqin Yu ,&nbsp;Jinqi Hao ,&nbsp;Liquan Wang ,&nbsp;Ruize Qiu ,&nbsp;Xiuchun Wang ,&nbsp;Xiaoyu Wang ,&nbsp;Hongzhang Cao ,&nbsp;Jihai Shi","doi":"10.1016/j.bbrc.2025.152072","DOIUrl":"10.1016/j.bbrc.2025.152072","url":null,"abstract":"<div><div>This study investigates the anti-inflammatory mechanisms of luteolin-gadolinium rare earth complexes (LutGdRCS) in LPS-activated macrophages, focusing on lysine-acetylated protein regulation. Transcriptional (qPCR), proteomic (4D-DIA tandem mass spectrometry), and functional analyses revealed that LutGdRCS significantly downregulated pro-inflammatory mediators (iNOS, IL-6, IL-1β) and nitric oxide (NO) levels. Quantitative acetylome profiling identified 1260 lysine-acetylation sites across 796 proteins, with 775 upregulated and 485 downregulated sites. Key proteins—Eef2, Rpl5, and Atp5c1—emerged as central hubs in protein-protein interaction networks, while Atp5f1cK_89 was identified as a critical deacetylation site linked to mitochondrial ATP synthase activity. Subcellular localization analysis showed cytoplasmic (34.7 %), nuclear (34.1 %), and mitochondrial (10.6 %) enrichment of modified proteins. Pathway mapping highlighted LutGdRCS-driven modulation of NF-κB, JAK-STAT, oxidative phosphorylation, and nitrogen metabolism pathways. Bioinformatic clustering further revealed altered ubiquitin ligase activity, antioxidant responses, and ribosomal functions. These findings demonstrate that LutGdRCS attenuates inflammation by dynamically regulating lysine acetylation, particularly through mitochondrial energy metabolism and immune signaling pathways. The study positions LutGdRCS as a novel rare earth-based therapeutic candidate for inflammatory disorders, offering mechanistic insights into its acetylome-level anti-inflammatory effects.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"773 ","pages":"Article 152072"},"PeriodicalIF":2.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF2-driven upregulation of OAS3 promotes AML cell proliferation by modulating the JAK-STAT signaling pathway","authors":"Xi Zhang ,&nbsp;Liang Zhong ,&nbsp;Li Zhai ,&nbsp;Haitao Li ,&nbsp;Beizhong Liu","doi":"10.1016/j.bbrc.2025.152064","DOIUrl":"10.1016/j.bbrc.2025.152064","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) presents significant treatment challenges due to its heterogeneity and resistance to conventional therapies. This study explored the role of 2′-5′-oligoadenylate synthetase 3 (OAS3) in AML progression and its potential as a prognostic and therapeutic biomarker. Through bioinformatics analysis, OAS3 was found to be significantly upregulated in AML patients and associated with poor clinical outcomes. Functional assays in AML cell lines revealed that silencing OAS3 suppressed cell proliferation, induced G1 phase arrest, and promoted apoptosis, while its overexpression enhanced cell growth. Pathway analysis and western blotting demonstrated that OAS3 regulates the JAK-STAT signaling pathway. Further investigation revealed that interferon regulatory factor 2 (IRF2) acts as a transcription factor that binds to the promoter region of OAS3 and enhances its expression, thereby indirectly modulating the JAK-STAT pathway. Cotransfection experiments with IRF2 and si-OAS3 supported this regulatory mechanism. In vivo studies using a xenograft model and subsequent immunohistochemical analysis of tumor specimens confirmed the role of OAS3 in AML progression. These findings highlight OAS3 as a critical player in AML pathogenesis, functioning through the JAK-STAT pathway activation under the transcriptional control of IRF2. The study suggests that OAS3 could serve as a valuable prognostic marker and therapeutic target, offering a promising avenue to improve AML treatment outcomes.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"772 ","pages":"Article 152064"},"PeriodicalIF":2.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Sine Oculis Homeobox Homolog 2 in colon Cancer: Insights into prognosis, immune regulation, and therapeutic implications","authors":"Shicheng Zhou ,&nbsp;Dan Jiang ,&nbsp;Yu Liu ,&nbsp;Qin Wang ,&nbsp;Manyi Hu ,&nbsp;Kangfu Dai ,&nbsp;Lin Chen ,&nbsp;Tianming Zhang ,&nbsp;Cheng Cai ,&nbsp;Jianping Wang","doi":"10.1016/j.bbrc.2025.152038","DOIUrl":"10.1016/j.bbrc.2025.152038","url":null,"abstract":"<div><div>Colon cancer (CC) remains a significant global health burden, and the search for novel prognostic biomarkers and therapeutic targets is crucial. This study comprehensively analyzed the role of SIX2 (Sine Oculis Homeobox Homolog 2) in CC. Utilizing data from TCGA, GTEx, and CCLE databases, differential expression of SIX2 was observed in multiple cancers, with significant upregulation in many tumors compared to normal tissues. In CC, SIX2's differential expression was notable. Cox regression analysis revealed its prognostic significance, with overexpression associated with poor survival outcomes. SIX2 was strongly associated with gene alterations and correlated with key signaling pathways like WNT and TGF-β. In the tumor microenvironment, SIX2 was related to immune cell infiltration and immune-related molecules. Notably, in CC, it was associated with immunosuppressive cells and checkpoint molecules. Additionally, ABT737 was found to sensitize tumor immunotherapy in the context of SIX2. Animal experiments demonstrated that ABT737 effectively restricted the growth of CC in mice, and its combination with antiPD-1 immunotherapy was more effective. It could reduce the infiltration of CD163+ tumor-associated macrophages but without significantly increasing the infiltration of CD8⁺ T cells. Our findings suggest that SIX2 is a potential key player in CC, offering insights into future research and the development of targeted therapies.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"772 ","pages":"Article 152038"},"PeriodicalIF":2.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}