Experimental cell research最新文献

{"title":"The combinations of histone lysine demethylase inhibitors with panobinostat exert enhanced effects against head and neck cancer cells.","authors":"Dawid Dorna, Robert Kleszcz, Karolina Drabarz, Małgorzata Kubiak, Barbara Stefanska, Jarosław Paluszczak","doi":"10.1016/j.yexcr.2026.115042","DOIUrl":"https://doi.org/10.1016/j.yexcr.2026.115042","url":null,"abstract":"<p><p>The effectiveness of treatment of head and neck squamous cell carcinomas (HNSCC) is still unsatisfactory, and novel therapeutics could improve outcomes. Histone deacetylases (HDAC) and histone lysine demethylases (KDMs) emerged as important molecular targets in HNSCC. Moreover, joint inhibition of epigenetic targets may be therapeutically advantageous. Thus, the aim of this project was to evaluate the effects of combinations of panobinostat, a pan-HDAC inhibitor, with KDM4-6 inhibitors (KDMi), ML324, GSK-J4, and JIB-04. Experiments were performed in FaDu and SCC-152 cell lines. Resazurin and clonogenic assays were used to evaluate the cell viability and clonogenic potential, respectively. Apoptosis was assessed by flow cytometry after Annexin V staining. Flow-cytometric detection of γH2A.X was applied for DNA damage evaluation. Gene expression was quantified by qPCR. KDM proteins occupancy at gene promoters was measured by quantitative chromatin immunoprecipitation. KDMi enhanced the anticancer effects of panobinostat in HNSCC cell lines. The combinations of panobinostat with ML324 and JIB-04 synergistically reduced cell viability in FaDu and SCC-152 cells, and increased apoptosis induction in SCC-152 cells. These effects could be attributed to the modulation of BIRC5 and CDKN2A expression, and enhanced accumulation of DNA double-strand breaks following combinatorial treatments in FaDu cells. Decreased expression of stemness-related genes upon KDMi treatment in FaDu cells was associated with decreased binding of KDM4A and/or KDM6B at SOX2 and POU5F1 gene promoters. The suppression of stemness-associated phenotype, and the concurrent promotion of apoptosis by the studied combinations of chemicals, suggest their potential as a novel therapeutic strategy in HNSCC.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115042"},"PeriodicalIF":3.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766815","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":"Role of CIRP in glioma Progression: Inhibition of ferroptosis via UBR5-Mediated ACSL4 degradation","authors":"Zhiyin Pang ,&nbsp;Xingwang Zu ,&nbsp;Ying Yang ,&nbsp;Pingping Yan ,&nbsp;Huicong Wang ,&nbsp;Junjie Liu ,&nbsp;Jinmin Hao","doi":"10.1016/j.yexcr.2026.114942","DOIUrl":"10.1016/j.yexcr.2026.114942","url":null,"abstract":"<div><div>Glioma represents the most aggressive form of primary brain tumor, characterized by restricted therapeutic strategies and unfavorable survival rates. Accumulating studies indicate that ferroptosis is critically involved in the advancement of glioma. Although cold-inducible RNA-binding protein (CIRP), an RNA chaperone protein, upregulated in various malignancies, has not been thoroughly investigated in glioma. This research revealed that CIRP is a significantly upregulated gene in glioma patients, with high expression correlating with worse prognosis. Through functional experiments, we demonstrated that CIRP enhances proliferative, migratory, and invasive capacities of glioma cells. Notably, we discovered that CIRP enhanced GBM cell resistance to ferroptosis, as evidenced by reduced intracellular iron levels, decreased lipid peroxidation, and elevated antioxidant capacity. Mechanistic studies revealed that CIRP facilitated the interaction between the E3 ubiquitin ligase UBR5 and ACSL4, leading to increased ubiquitination and subsequent proteasomal degradation of ACSL4. In summary, our findings indicate that CIRP advances glioma progression via inhibiting ferroptosis through the promotion of UBR5-mediated ACSL4 degradation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 2","pages":"Article 114942"},"PeriodicalIF":3.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194346","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":"Temporal modulation of cuproptosis and autophagy mediates nanographene-driven pulmonary fibrosis progression","authors":"Jiarui Xia ,&nbsp;Xiaolong Tang ,&nbsp;Huijie Shang ,&nbsp;Youliang Zhao ,&nbsp;Shuqi Li ,&nbsp;Ke Tang ,&nbsp;Yi Li ,&nbsp;Wenzhuo Wu ,&nbsp;Qun Xu ,&nbsp;Changfu Hao ,&nbsp;Wu Yao","doi":"10.1016/j.yexcr.2026.114927","DOIUrl":"10.1016/j.yexcr.2026.114927","url":null,"abstract":"<div><div>Graphene nanoparticles are increasingly used in materials manufacturing, pollutant treatment, energy storage, and electronic devices, and the potential risk of occupational and environmental exposure is a concern. The mechanisms of lung fibrosis induced by nano-graphene with different properties are complex. In addition, multiple modes of programmed cell death (PCD) occur during lung fibrosis, and whether cuproptosis and autophagy exert regulatory effects during the progression of lung fibrosis induced by nano-graphene remains undocumented. In this study, we constructed mouse models with varying doses of graphene and exposure durations. We observed the dynamics of pathological changes in lung histology and the time-series expression of biomarkers. We discovered that graphene could deposit in lung tissue, leading to the pathological manifestations of pulmonary fibrosis; this was coincident with elevated copper ion concentration, cellular cuproptosis, and excessive autophagy. In short, our results may contribute to further elucidation of the potential respiratory toxic effects and mechanisms of graphene, and to the early development of targeted preventive and control measures by providing new ideas and reference points.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 1","pages":"Article 114927"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122739","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":"Insulin-like growth factor-1 enhances β-amyloid protein clearance in HMC3 microglia via low-density lipoprotein receptor-related protein 1-mediated pathway","authors":"Hongsong Guo,&nbsp;Xiaoqian Peng,&nbsp;Xiao Zhang,&nbsp;John Bosco Ruganzu,&nbsp;Xiangyuan Wu,&nbsp;Mingtao Zhao,&nbsp;Pengbo Yang,&nbsp;Shengfeng Ji,&nbsp;Weina Yang","doi":"10.1016/j.yexcr.2026.114920","DOIUrl":"10.1016/j.yexcr.2026.114920","url":null,"abstract":"<div><div>β-amyloid protein (Aβ) deposition occurs years before cognitive symptoms appear and is considered one of the main causes underlying the pathogenic events that occur in Alzheimer's disease (AD). Mounting evidence suggests that the imbalance of Aβ production and clearance leads to the accumulation of Aβ and the subsequent formation of toxic Aβ aggregates. Aβ is internalized by microglia and transported to lysosomes for degradation, which is one of the main ways by which Aβ may be cleared from the brain. Insulin-like growth factor-1 (IGF-1) promotes clearance of Aβ in the brain by enhancing Aβ carrier proteins. Our previous study demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) mediates the internalization of Aβ_1-42 and lysosomal trafficking in primary cortical neurons. However, whether IGF-1 enhances the clearance of Aβ in microglia through the LRP1-mediated pathway and its underlying mechanisms is incompletely understood. Here, we reported that knockdown of LRP1 expression significantly decreased the internalization of Aβ_1-42 in HMC3 cells. Furthermore, pretreatment with IGF-1 significantly increased intracellular Aβ_1-42, indicating IGF-1 enhances HMC3 cells uptake of extracellular Aβ_1-42. Interestingly, the intracellular Aβ_1-42 in LRP1-knockdown HMC3 cells was reduced after preincubation with IGF-1. Thus, it was indicated that LRP1 is essential for IGF-1-enhanced internalization of Aβ_1-42 in HMC3 cells. Moreover, IGF-1 significantly inhibited the downregulation of PI3K, phospho-PI3K, Akt, and phospho-Akt induced by Aβ_1-42. Importantly, treatment with LY294002, a PI3K inhibitor, significantly reduced the intracellular Aβ_1-42 levels and decreased the expression of LRP1. These findings indicated that IGF-1 enhances the internalization of Aβ in a LRP1-dependent manner by activating the PI3K/Akt signaling pathway. Finally, we identified that IGF-1 promotes lysosomal proteolysis of Aβ_1-42 by increasing cathepsin B (CTSB) and cathepsin D (CTSD) expression. Consequently, these results demonstrated that IGF-1 promotes the internalization and lysosomal degradation of Aβ by microglia, which is an effective approach to lowering brain Aβ levels, and it might be a promising therapeutic target for AD.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 1","pages":"Article 114920"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100148","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":"AHNAK inhibits osteoporosis progression by stabilizing Smad1 protein","authors":"Weifei Zhang ,&nbsp;Hua Chen ,&nbsp;Tiantian Qi ,&nbsp;Dengbo Yao ,&nbsp;Hang Liu ,&nbsp;Hui Zeng ,&nbsp;Fei Yu ,&nbsp;Wenyu Zhou","doi":"10.1016/j.yexcr.2026.114899","DOIUrl":"10.1016/j.yexcr.2026.114899","url":null,"abstract":"<div><div>AHNAK is a structural scaffold protein implicated in a wide array of physiological functions. AHNAK mutations are highly prevalent in patients with osteoporosis, However, it is currently unknown whether AHNAK affects the progression of osteoporosis and the specific mechanism behind this effect. This study detected decreased AHNAK (AHNAK1) expression in bone tissues and bone marrow mesenchymal stem cells (BMSCs) of osteoporotic mice. Genetic knockdown of AHNAK inhibited osteogenic differentiation of BMSCs. Mechanistic investigations indicated that AHNAK functions through stabilizing Smad1 protein levels. Overexpression of Smad1 in AHNAK-knockdown BMSCs restored their osteogenic differentiation capacity. Furthermore, in vivo mouse experiments further confirmed these findings. Collectively, these findings indicate that AHNAK inhibits the progression of osteoporosis by stabilizing Smad1 protein.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114899"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003459","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 Runx2 switch: unlocking osteoblast-related disorders through signaling pathways and non-coding RNAs","authors":"Somayeh Aslani ,&nbsp;Ashkan Kalantary-Charvadeh ,&nbsp;Roghayeh Abbasalipourkabir ,&nbsp;Nasrin Ziamajidi","doi":"10.1016/j.yexcr.2026.114921","DOIUrl":"10.1016/j.yexcr.2026.114921","url":null,"abstract":"<div><div>Osteoblasts, specialized bone-forming cells, differentiate from mesenchymal stem cells (MSCs). In recent years, stem cell-derived osteoblasts have emerged as potential choices for the treatment of bone-related disorders. A complex network of regulatory elements, including signaling pathways, transcription factors, and non-coding RNAs (ncRNAs), orchestrates MSCs differentiation. Among the key regulators of osteoblast differentiation is Runt-related transcription factor 2 (Runx2), a master transcription factor essential for osteogenic commitment. Elucidating the molecular mechanisms that regulate Runx2 expression and function is critical for the treatment of osteoblast-related disease. Runx2 is regulated through signaling pathways and a complex, post-transcriptional competing endogenous RNA (ceRNA) network. In this network, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) sequester microRNAs (miRNAs), thereby fine-tuning Runx2 expression. Signaling pathways can also indirectly regulate Runx2 by inducing the expression of osteo-regulatory miRNAs. This review highlights the regulatory role of Runx2 during osteoblastic differentiation. It also explores how signaling pathways, lncRNAs, circRNAs, and other factors interact with Runx2-regulatory miRNAs involved in this process.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114921"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100134","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":"KAT5/8-mediated GPX4 lactylation facilitates ferroptosis and inflammation in diabetic retinopathy","authors":"Yan Zhou,&nbsp;Min Du","doi":"10.1016/j.yexcr.2026.114915","DOIUrl":"10.1016/j.yexcr.2026.114915","url":null,"abstract":"<div><div>Diabetes-induced hyperglycemia promotes retinal capillary endothelial cell dysfunction, contributing to diabetic retinopathy. In this study, we reveal that high glucose (HG) drives ferroptosis and inflammation through lactate-mediated GPX4 lactylation. HG conditions enhance glycolysis and lactate production, leading to increased lactylation of GPX4, a process mediated by the acetyltransferases KAT5 and KAT8. GPX4 lactylation reduces its antioxidant function, promoting lipid peroxidation, ferroptosis, and inflammation. Specifically, HG exposure significantly increases malondialdehyde (MDA) levels, decreases GSH levels, and elevates lipid ROS, while simultaneously inducing pro-inflammatory cytokine expression (<em>IL6</em>, <em>TNF</em>, and <em>IL1B</em>). Inhibition of KAT5 and KAT8 markedly reduces GPX4 lactylation, restores redox balance, suppresses ferroptosis, and mitigates inflammation. Collectively, our findings identify KAT5- and KAT8-mediated GPX4 lactylation as a key mechanism underlying HG-induced ferroptosis and inflammation in diabetic retinopathy, highlighting its potential as a promising therapeutic target.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114915"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092382","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":"CDC6 promotes keratinocyte senescence through the CCND1/P53 signaling in ischemia-reperfusion injury-induced pressure injury","authors":"Chenming Wang ,&nbsp;Shanshan Zhu ,&nbsp;Meige Dai ,&nbsp;Hui Chen","doi":"10.1016/j.yexcr.2026.114903","DOIUrl":"10.1016/j.yexcr.2026.114903","url":null,"abstract":"<div><div>Pressure injuries develop when prolonged compression of the skin and subcutaneous tissue impairs blood circulation, leading to localized tissue ischemia, degeneration, and ultimately necrosis. Ischemia-reperfusion(I/R) injury is one of the key pathological mechanisms underlying pressure injury formation. While cellular senescence has been implicated in I/R-related pathologies, its role in pressure injury development remains unclear. We aimed to elucidate the mechanisms of keratinocyte senescence in cutaneous I/R injury. An in vitro hypoxia/reoxygenation (H/R) model was employed to simulate I/R injury using human immortalized keratinocytes (HaCaT). H/R induction significantly exacerbated the senescence response, as characterized by reduced cell proliferation, increased apoptosis, elevated SA-β-galactosidase (SA-β-gal) activity, and upregulated expression of senescence markers (p16 and p21). Quantitative proteomic analysis identified CDC6 as a prominently upregulated protein under H/R conditions. siRNA-mediated CDC6 knockdown attenuated keratinocyte senescence, restored G1/S phase cyclin-D1 (CCND1) expression, and suppressed p53 levels, demonstrating its regulatory role in senescence via the p53/CCND1 pathway. Furthermore, protein interaction network analysis and experimental validation revealed CDC6's direct binding with origin recognition complex 2 (ORC2), evidenced by nuclear colocalization (immunofluorescence) and physical interaction (co-immunoprecipitation). Collectively, our findings pioneers the mechanistic elucidation of CDC6 in pressure injury pathology, proposing senescence-targeted interventions as a novel therapeutic strategy for ulcer management.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114903"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043768","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":"Corrigendum to “A human tissue-based model of renal inflammation” [Exp. Cell Res. 2024 Nov 1;443(1):114309]","authors":"Camilla Merrild ,&nbsp;Gitte A. Pedersen ,&nbsp;Kristian W. Antonsen ,&nbsp;Mia G. Madsen ,&nbsp;Anna K. Keller ,&nbsp;Holger J. Møller ,&nbsp;Lene N. Nejsum ,&nbsp;Henricus A.M. Mutsaers ,&nbsp;Rikke Nørregaard","doi":"10.1016/j.yexcr.2026.114896","DOIUrl":"10.1016/j.yexcr.2026.114896","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114896"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028819","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":"Overexpression of biliverdin reductase A leads to ROS-independent sensitization of ovarian adenocarcinoma cells to gemcitabine","authors":"Zuzana Solárová ,&nbsp;Kristína Danková ,&nbsp;Pavol Harvanik ,&nbsp;Peter Bober ,&nbsp;Petra Majerová ,&nbsp;Radka Michalková ,&nbsp;Mangesh Bhide ,&nbsp;Peter Solár","doi":"10.1016/j.yexcr.2026.114905","DOIUrl":"10.1016/j.yexcr.2026.114905","url":null,"abstract":"<div><h3>Aims</h3><div>Biliverdin reductase A (BLVRA) is a key enzyme in bilirubin metabolism, where it reduces biliverdin to bilirubin. Bilirubin is a potent antioxidant that protects cells from oxidative stress. Therefore, reduced or deregulated BLVRA activity may contribute to increased oxidative DNA damage, which is one of the factors leading to the neoplastic transformation of cells.</div></div><div><h3>Methods</h3><div>Human ovarian adenocarcinoma A2780 cells were transfected with a PiggyBac vector to achieve BLVRA overexpression. A2780 clones showing the most significant BLVRA gene overexpression were analyzed by proteomics and flow cytometry to assess rective oxygen species (ROS) production.</div></div><div><h3>Results</h3><div>Our results indicate that BLVRA overexpression increases the sensitivity of A2780 cells to doxorubicin and gemcitabine, with the most pronounced effect observed in the J clone. In this clone, the highest level of BLVRA overexpression correlated with significant alterations in the p53 signaling pathway. Upregulation of key effectors such as Bax and CDKN2A indicates a potential role for BLVRA in promoting pro-apoptotic responses. Moreover, <em>BLVRA</em> overexpression increased the sensitivity of A2780 cells to gemcitabine independently of ROS.</div></div><div><h3>Conclusions</h3><div>This study broadens our understanding of BLVRA in ovarian cancer. In cells with intact p53 signaling, BLVRA overexpression can paradoxically enhance cytotoxic response to certain drugs, particularly gemcitabine.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114905"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046340","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}