Molecular and Cellular Biochemistry最新文献

{"title":"14-3-3ζ: an optimal housekeeping protein for western blot analysis in swine rotator cuff tendon studies.","authors":"Resmi Rajalekshmi, Vikrant Rai, Devendra K Agrawal","doi":"10.1007/s11010-025-05255-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05255-6","url":null,"abstract":"<p><p>Healthy biomechanics of the shoulder involving rotator cuff muscles and rotator cuff tendon (RCT) is pivotal for joint stability, yet co-morbid conditions like hyperlipidemia and hyperglycemia can lead to degenerative changes jeopardizing tendon integrity. A change in protein expression, the functional moiety for molecular events, may result in altered healing of RCT and prolonged morbidity. Expression and activity of proteins are critical while investigating the underlying molecular and cellular changes involved in tendinopathy. While investigating the changes in the protein expression of various inflammatory mediators, we observed that the Western Blot bands for commonly used housekeeping genes (GAPDH, β-actin, and α-tubulin) were not uniform in different tendon samples. Therefore, we investigated for an optimal housekeeping gene for Western blot analysis in swine RCT under normal and hyperlipidemic conditions, as this is essential for accurate normalization of protein expression. The study evaluated several housekeeping genes-GAPDH, beta-actin, alpha and beta-tubulin, Ubiquitin C, Cyclophilin A, TATA-box binding protein, and 14-3-3ζ-to ensure robust normalization across experimental setups. The results revealed that the protein expression of 14-3-3ζ was uniform in all samples, thereby validating its suitability as a stable housekeeping protein. The findings are important while studying the RCT pathology in a clinically relevant animal model, like swine, which mimics human RCT and provides translationally significant findings. Thus, the 14-3-3ζ protein will be an ideal housekeeping gene in the design of experiments utilizing musculoskeletal tissues.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692573","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":"Histone H2A: a promising diagnostic marker in heart failure with reduced versus preserved ejection fraction.","authors":"Desislava K Tsoneva, Diana Buzova, Salvatore Daniele Bianco, Antoniya Kisheva, Mesut Rushid, Tanya Ivanova, Yoto Yotov, Jan Cerveny, Tommaso Mazza, Manlio Vinciguerra","doi":"10.1007/s11010-025-05254-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05254-7","url":null,"abstract":"<p><p>The diagnosis of heart failure with preserved left ventricle ejection fraction (HFpEF) remains a challenge, with score-based algorithms showing varying diagnostic performance and biomarkers sometimes inconclusive. This study aimed to examine whether circulating histones and histone complexes, which recently emerged as robust biomarkers of inflammation and stroke, show distinct profiles in plasma from healthy individuals, HF with reduced EF (HFrEF), and HFpEF patients. We evaluated the plasma histone profile of 30 sex/age-matched healthy individuals, 22 HFpEF and 25 HFrEF prior any therapeutic intervention. ImageStreamX-based detection approach was used to measure the levels of circulating particles positive for core histones H2A, H2B, H3, H4, histone variants macroH2A1.1 and macroH2A1.2. While we found increased levels of most of the histones and histone complexes in both HFpEF and HFrEF patients, H2A was significantly elevated only in HFpEF, compared to healthy individuals (p-value = 0.002) and to HFrEF (p-value = 0.00008). In line with these findings, H2A showed positive correlation with EF (r = 0.493). We identified a plasma histone profile able to detect HF and differentiate between HFpEF and HFrEF using a high throughput and imaging flow cytometry-adapted liquid biopsy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692714","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":"LncRNA BDNF-AS binds to DNMT1 to suppress angiogenesis in glioma by promoting NEDD4L-mediated YAP1 ubiquitination.","authors":"Yongwen Deng, Jixin Feng, Jiangyang Li, Shuhui Gong, Shengli Sun","doi":"10.1007/s11010-025-05250-x","DOIUrl":"https://doi.org/10.1007/s11010-025-05250-x","url":null,"abstract":"<p><p>Glioma, a highly aggressive brain tumor, is characterized by high mortality and frequent recurrence rates. Angiogenesis is a critical hallmark of glioma progression. However, the regulatory role and underlying mechanism of lncRNA brain-derived neurotrophic factor-antisense (BDNF-AS) in glioma angiogenesis remain poorly understood and warrant further investigation. Malignant characteristics of glioma cells were evaluated using CCK-8, colony formation, scratch, transwell, flow cytometry, and tube formation assays. The expression levels of genes and proteins were detected by RT-qPCR, western blot, and IHC assays. The methylation level of NEDD4-like E3 ubiquitin protein ligase (NEDD4L) was determined using MSP. The interactions among molecules were validated using RIP, ChIP, and Co-IP. Our study revealed significantly downregulated BDNF-AS expression in glioma cells. BDNF-AS overexpression markedly attenuated the malignant characteristics of glioma cells, as evidenced by decreased viability, proliferation, migration, invasion, and angiogenesis, along with increased apoptosis. These tumor-suppressive effects were significantly abrogated by NEDD4L knockdown. Mechanistically, BDNF-AS could interact with DNA methyltransferase 1 (DNMT1) expression, leading to reduced NEDD4L promoter methylation and upregulation of NEDD4L expression. Additionally, NEDD4L-mediated promotion of YAP1 ubiquitination to decline YAP1 and VEGFA expression. Finally, BDNF-AS exerted potent anti-tumor effects by mediating NEDD4L/YAP1/VEGFA axis, as demonstrated by suppressed tumor growth in glioma-bearing mice and attenuated malignant features in glioma cells. BDNF-AS suppressed cell viability, proliferation, migration, and invasion, and promoted cell apoptosis of glioma cells, attenuated angiogenesis of human umbilical vein endothelial cells (HUVECs), and tumor growth via regulating NEDD4L/YAP1/VEGFA axis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677129","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":"Exploring exhaled volatile organic compounds as potential biomarkers in anti-MDA5 antibody-positive interstitial lung disease.","authors":"Yuxuan Wang, Xuewen Wang, Luqin Yang, Ke Wang, Fengqin Zhang, Huihui Yue, Junqi Wang, Minhua Peng, Pengnan Fan, Xiangcheng Qiu, Han Zhang, Wei Lin, Yuhang Lin, Sitong Chen, Qian Geng, Chaotan Sima, Deming Liu, Ping Lu, Huilan Zhang","doi":"10.1007/s11010-025-05249-4","DOIUrl":"https://doi.org/10.1007/s11010-025-05249-4","url":null,"abstract":"<p><p>Interstitial lung diseases (ILDs) are a group of pulmonary disorders characterized by fibrosis, inflammation, and lung tissue deterioration. Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5-ILD), a subtype, is associated with high mortality due to rapid progression and severe lung damage. Volatile organic compounds (VOCs) in exhaled breath, reflecting metabolic changes, have been identified as potential non-invasive biomarkers for various diseases, including respiratory conditions. However, their role in MDA5-ILD has not been extensively studied. This retrospective cohort study included 45 exhaled breath samples from 19 ILD patients, with 31 samples from 9 patients with MDA5-ILD and 10 samples from 7 patients with non-MDA5-ILD. VOCs were collected using thermal desorption tubes and analyzed via gas chromatography-mass spectrometry (GC-MS). Clinical data, including the APACHE II score, were integrated with VOC profiles. Two logistic regression models were developed: Model 1 based on 11 clinical indicators, and Model 2 integrating 11 clinical indicators with 5 VOC features. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, sensitivity, specificity, and accuracy metrics. Five VOCs-N-(2-Aziridinyl)ethanamine, Cyclohexanone, Nonanal, Dodecamethylcyclohexasiloxane, and 4-Methyltetradecane-were identified as significant biomarkers distinguishing MDA5-ILD from non-MDA5-ILD. Model 2, which integrated VOC data, outperformed Model 1, achieving an area under the curve (AUC) of 0.93 compared to 0.70. Model 2 also demonstrated enhanced accuracy (84.6% vs. 76.9%), specificity (66.7% vs. 33.3%), precision (90.0% vs. 81.8%), and F1-score (90.0% vs. 85.7%). Additionally, 1,3-Pentadiene and 3-Methylundecane were identified as potential markers of disease severity, with 1,3-Pentadiene negatively correlating and 3-Methylundecane positively correlating with both APACHE II scores and creatinine levels. VOCs in exhaled breath significantly enhance the diagnostic sensitivity and accuracy for detecting MDA5-ILD. In addition, VOCs show promise as disease severity markers, potentially aiding in the assessment of disease severity and progression. While the integration of VOCs holds great potential for improving diagnostic performance, further validation through larger, multicenter studies is necessary.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657658","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":"Skin regenerative potential of hydrogel matrices incorporated with stem cell-derived extracellular vesicles enriched with MicroRNAs: a systematic review.","authors":"Xiaolei Miao, Maryam Davoudi, Sahar Sadegh-Nejadi, Seyed Arsalan Ghahari, Molood Bagherieh, Reza Afrisham","doi":"10.1007/s11010-025-05248-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05248-5","url":null,"abstract":"<p><p>Stem cell-derived extracellular vesicles (SC-EVs) are one huge promise in skin regenerative medicine, similar in advantages to stem cells with low immunerejection and tumor formations. These microvesicles are laden with microRNAs, which assist in wound healing via angiogenesis and immune modulation. However, quick degradation and poor cellular uptake limit their regenerative capacity. Thanks to their adjustable characteristics, hydrogels can act as vehicles for transporting and sustainably releasing miRNA-SC-EVs at injury sites. Therefore, a systematic literature review was conducted on miRNA-enriched SC-EVs incorporated into hydrogels in animal skin regeneration models published from 2010 to 2024 (PROSPERO ID: CRD42024588072). Out of the 89 records, 12 met the criteria. Diabetic wounds are characterized by chronic inflammation, oxidative stress, and defective macrophage polarization, resulting in less satisfactory regeneration. The hydrogels tackled these issues by shifting macrophages from a pro-inflammatory M1 phenotype to a healing M2 phenotype, promoting collagen production, enhancing fibroblast movement, and boosting angiogenesis. Burn injuries frequently lead to slow recovery due to hypertrophic scarring, extended inflammation, and infection. Hyaluronic acid (HA)-derived hydrogels, infused with miR-21-5p and surface-treated with polydopamine and cationic antimicrobial peptides, promoted wound healing by lowering scarring and demonstrating anti-inflammatory, anti-apoptotic, and pro-angiogenic characteristics. The cell adhesion of these hydrogels can be enhanced by adding MOFs, chitosan, and extracellular matrix elements. The application of stimulus-responsive or stage-specific hydrogels is another mode of targeted healing. Further research and clinical trials will enhance the wound-healing efficiency of hybrid hydrogels.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of mitochondrial dysfunction in the protective effect of ginger derived extracellular vesicles on hepatic stellate cells against cytotoxicity.","authors":"Jing Yang, Yujie Yang, Xiqian Zhang, Yuan Qin, Toshihiro Sato, Shuyun Qing, Yirong Wang, Xiang Ye, Min Xu, Ying Liu, Qin He, Yaxian Zheng","doi":"10.1007/s11010-025-05232-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05232-z","url":null,"abstract":"<p><p>Previous studies have shown that ginger-derived extracellular vesicles (Gin-EVs) can alleviate alcohol-induced liver injury. It remained unknown and needs to be further verified that whether the vesicles has therapeutic potential to alleviate the progression of liver fibrosis. Moreover, the relevant mechanisms need to be further studied. Herein, we provide evidence that Gin-EVs effectively interact with human hepatic stellate cells (LX-2), offering protection against carbon tetrachloride (CCL4) or lipopolysaccharides (LPS)-induced liver fibrosis. The treatment with Gin-EVs was observed to mitigate fibrosis and enhance cell viability in LX-2 cells exposed to CCL4 or LPS. Mechanistically, Gin-EVs counteracted mitochondrial dysfunction by restoring mitochondrial dynamics imbalance characterized by enhanced fusion and reduced fission events while promoting mitochondrial biogenesis, thereby potentially preventing fibrotic processes in LX-2 cells. Collectively, the findings highlight the direct cytoprotective effects of Gin-EVs on LX-2 cells and suggest their promising role as a therapeutic option for hepatic fibrosis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649380","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":"Cardiomyocyte regeneration after infarction: changes, opportunities and challenges.","authors":"Ce Cao, Lili Yang, Jianshu Song, Zixin Liu, Haoran Li, Lei Li, Jianhua Fu, Jianxun Liu","doi":"10.1007/s11010-025-05251-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05251-w","url":null,"abstract":"<p><p>Myocardial infarction is a cardiovascular disease that poses a serious threat to human health. The traditional view is that adult mammalian cardiomyocytes have almost no regenerative ability, but recent studies have shown that they have regenerative potential under specific conditions. This article comprehensively describes the research progress of post-infarction cardiomyocyte regeneration, including the characteristics of cardiomyocytes and post-infarction changes, regeneration mechanisms, influencing factors, potential therapeutic strategies, challenges and future development directions, and deeply discusses the specific pathways and targets included in the regeneration mechanism, aiming to provide new ideas and methods for the treatment of myocardial infarction.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649364","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":"Insulin resistance and cancer: molecular links and clinical perspectives.","authors":"Alfredo Caturano, Enes Erul, Roberto Nilo, Davide Nilo, Vincenzo Russo, Luca Rinaldi, Carlo Acierno, Maria Gemelli, Riccardo Ricotta, Ferdinando Carlo Sasso, Antonio Giordano, Caterina Conte, Yüksel Ürün","doi":"10.1007/s11010-025-05245-8","DOIUrl":"https://doi.org/10.1007/s11010-025-05245-8","url":null,"abstract":"<p><p>The association between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cancer is increasingly recognized and poses an escalating global health challenge, as the incidence of these conditions continues to rise. Studies indicate that individuals with T2DM have a 10-20% increased risk of developing various solid tumors, including colorectal, breast, pancreatic, and liver cancers. The relative risk (RR) varies depending on cancer type, with pancreatic and liver cancers showing a particularly strong association (RR 2.0-2.5), while colorectal and breast cancers demonstrate a moderate increase (RR 1.2-1.5). Understanding these epidemiological trends is crucial for developing integrated management strategies. Given the global rise in T2DM and cancer cases, exploring the complex relationship between these conditions is critical. IR contributes to hyperglycemia, chronic inflammation, and altered lipid metabolism. Together, these factors create a pro-tumorigenic environment conducive to cancer development and progression. In individuals with IR, hyperinsulinemia triggers the insulin-insulin-like growth factor (IGF1R) signaling pathway, activating cancer-associated pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PIK3CA), which promote cell proliferation and survival, thereby supporting tumor growth. Both IR and T2DM are linked to increased morbidity and mortality in patients with cancer. By providing an in-depth analysis of the molecular links between insulin resistance and cancer, this review offers valuable insights into the role of metabolic dysfunction in tumor progression. Addressing insulin resistance as a co-morbidity may open new avenues for risk assessment, early intervention, and the development of integrated treatment strategies to improve patient outcomes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634292","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":"ZnT6-mediated Zn²⁺ redistribution: impact on mitochondrial fission and autophagy in H9c2 cells.","authors":"Erkan Tuncay, Yusuf Olgar, Leila Aryan, Suatnur Şık, Deniz Billur, Belma Turan","doi":"10.1007/s11010-025-05247-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05247-6","url":null,"abstract":"<p><p>Cytosolic free Zn²⁺ level ([Zn²⁺]_Cyt) is tightly regulated by Zn²⁺ transporters, under both physiological and pathological conditions. At the cellular level, dysregulated free Zn²⁺ levels have been linked to metabolic and cardiovascular diseases, primarily through their association with various Zn²⁺ transporters. However, the role and localization of ZnT6 in cardiomyocytes remain unclear. Previous studies have shown a significant increase in ZnT6 expression in insulin-resistant cardiomyocytes, suggesting a potential link between ZnT6 dysregulation and cardiac cell dysfunction. Therefore, here, we investigated the impact of ZnT6 overexpression (ZnT6-OE) on cellular Zn²⁺ distribution, mitochondrial dynamics, and autophagy-induced apoptosis in H9c2 cardiomyocytes. Using confocal imaging, biochemical assays, and electron microscopy, we demonstrated the mitochondrial localization of ZnT6 and its role in H9c2 cells. Our findings showed that ZnT6 overexpression led to a significant increase in mitochondrial free Zn²⁺ level ([Zn²⁺]_Mit) with a significant reduction in [Zn²⁺]_Cyt, which seems to be associated with enhanced numbers of mitochondria and mitochondrial fission process. Specifically, the ZnT6-OE cells exhibited increased dynamin-related protein 1 (DRP1) translocation to mitochondria which is an indication of excessive fission activity. We also determined severe mitochondrial dysfunction in ZnT6-OE cells, such as depolarization in mitochondrial membrane potential, production of excessive reactive oxygen species (ROS), reduced ATP levels, and autophagosome accumulation. Furthermore, these impairments were accompanied by elevated apoptotic markers, indicating autophagy-induced apoptosis. Our findings highlight ZnT6 as a critical regulator of mitochondrial dynamics and function in cardiomyocytes, contributing to disruption Zn²⁺ homeostasis by its overexpression, triggering excessive DRP1-mediated mitochondrial fission and leading to mitochondrial dysfunction, oxidative stress, and apoptotic cell death, suggesting an important impact of ZnT6 dysregulation on cardiomyocyte pathophysiology in metabolic disorders.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634298","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":"STAT1 increases the sensitivity of lung adenocarcinoma to carbon ion irradiation via HO-1-mediated ferroptosis.","authors":"Yanliang Chen, Dandan Wang, Hongtao Luo, Mingyu Tan, Qian Wang, Xun Wu, Tianqi Du, Qiuning Zhang, Wenzhen Yuan","doi":"10.1007/s11010-025-05240-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05240-z","url":null,"abstract":"<p><p>Radiotherapy is a vital treatment agent for lung adenocarcinoma (LUAD) patients, while radioresistance remains a major factor in treatment failure. Here, we aimed to elucidate how signal transducer and activator of transcription 1 (STAT1) affected sensitivity to carbon ion irradiation for LUAD cells in vivo and in vitro. The results of colony formation, CCK-8, EdU, and calcein-AM/PI double-staining assays demonstrated that the overexpression of STAT1 markedly enhanced the inhibitory effect of carbon ion irradiation on the viability of LUAD cells (A549 and PC9 cells). Lactate dehydrogenase (LDH) leakage assays identified ferroptosis as the predominant form of cell death induced by STAT1 overexpression in LUAD cells. Meanwhile, the ferroptosis-related PCR array confirmed heme oxygenase 1 (HO-1) as a potential effector molecule of STAT1-induced ferroptosis. Mechanistically, STAT1 overexpression resulted in phosphorylation at the serine 727 residue, triggering the upregulation of HO-1 expression and subsequent labile iron pool (LIP) accumulation. This process amplified the Fenton reaction, leading to increased reactive oxygen species (ROS), lipid peroxides (LPO), and glutathione (GSH) depletion. HO-1 knockdown eliminated the ferroptosis induced by the overexpression of STAT1. Furthermore, in vivo experiments showed that STAT1 overexpression enhanced the effect of carbon ion irradiation in inhibiting the growth of subcutaneous tumors in nude mice. These findings provide the foundation for the development of the STAT1-HO-1 axis as a radiosensitization target for LUAD patients.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634297","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}