Experimental cell research最新文献

{"title":"SLC25A40 promotes NSCLC growth by enhancing NADPH-mediated lipid synthesis and suppressing ROS accumulation-induced ferroptosis","authors":"Peini Xue ,&nbsp;Xian Guo ,&nbsp;Boru Zhang ,&nbsp;Xin Yang ,&nbsp;Jiaying Gao ,&nbsp;Feng Zhou ,&nbsp;Jiangang Ma ,&nbsp;Faguang Jin","doi":"10.1016/j.yexcr.2025.114727","DOIUrl":"10.1016/j.yexcr.2025.114727","url":null,"abstract":"<div><div>Mitochondria serve as vital organelles that play critical roles in regulating cell metabolism and maintaining redox homeostasis. Their dysfunctions are closely associated with the progression of multiple human malignancies. SLC25A40 has been predicted as a mitochondrial carrier required for glutathione import into mitochondria. However, the role of SLC25A40 in human cancers, especially in non-small cell lung cancer (NSCLC), remains poorly understood. Here, we found that SLC25A40 expression was elevated in NSCLC. This upregulation was associated with poor prognosis. Silencing SLC25A40 suppressed NSCLC growth by inhibiting cell proliferation and inducing ferroptosis, whereas its overexpression promoted NSCLC growth. Mechanistically, SLC25A40 promotes cell proliferation by increasing NADPH-mediated lipid synthesis and suppresses ferroptosis by decreasing mitochondrial ROS accumulation. Furthermore, we demonstrated that the elevation of SLC25A40 expression in NSCLC cells was primarily due to decreased miR-4299. This research highlights the pivotal role of SLC25A40 in NSCLC progression by modulating both cell proliferation and ferroptosis, suggesting it as a promising therapeutic target in the management of NSCLC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 1","pages":"Article 114727"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933930","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":"PRDX3 promotes nasopharyngeal carcinoma tumor growth by regulating PINK1/Parkin pathway-dependent lipid peroxidation and mitochondrial dysfunction","authors":"Hualong Qiang ,&nbsp;Wei Wang ,&nbsp;Xiaodong Zhan ,&nbsp;Shiyin Ma","doi":"10.1016/j.yexcr.2025.114731","DOIUrl":"10.1016/j.yexcr.2025.114731","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) is a challenging malignancy characterized by aggressive progression and limited therapeutic efficacy. Emerging evidence implicates peroxiredoxin 3 (PRDX3), a mitochondrial peroxidase, as a critical regulator of redox homeostasis and mitochondrial integrity. Given its role in modulating cell death through mitochondrial quality control, we investigated the therapeutic potential of targeting PRDX3 in NPC.</div></div><div><h3>Methods</h3><div>PRDX3 expression patterns were assessed in clinical NPC specimens using immunohistochemical and immunoblotting. Functional studies employed siRNA-mediated PRDX3 knockdown followed by cellular assays: CCK-8 proliferation, clonogenic survival, and mitochondrial parameter quantification (reactive oxygen species flux using DCFH-DA/C11-BODIPY, ATP biosynthesis, membrane polarization, and mtDNA integrity). Molecular interplay between PRDX3 and PTEN-induced kinase 1 (PINK1) was elucidated through co-immunoprecipitation and immunofluorescence analysis. In vivo therapeutic efficacy was validated using a xenograft model to evaluate tumor growth modulation.</div></div><div><h3>Results</h3><div>Clinical specimens revealed significant PRDX3 overexpression in NPC compared to non-malignant controls. PRDX3 knockdown substantially attenuated malignant behavior and induced mitochondrial dysfunction in NPC cells. Mechanistically, PRDX3 interacted with PINK1 to stabilize Parkin-mediated mitophagic flux. PRDX3 safeguarded against apoptosis by sustaining PINK1/Parkin-dependent mitophagy clearance of damaged mitochondria. In vivo validation confirmed that PRDX3 knockdown suppressed tumor growth.</div></div><div><h3>Conclusion</h3><div>PRDX3 acts as an upstream activator of the PINK1/Parkin signaling cascade, regulating lipid peroxidation-mediated mitochondrial dysfunction, mitophagy, survival and apoptosis of NPC cell.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"452 1","pages":"Article 114731"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006020","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":"Inhibition of HMGN2 SUMOylation ameliorates atherosclerosis by activating PAX5 expression to induce macrophage M2 polarization","authors":"Xiangkui Wang ,&nbsp;Peipei Wu ,&nbsp;Yadi Shen ,&nbsp;Shiwei Xu ,&nbsp;Qi Wan ,&nbsp;Yongfei Yang","doi":"10.1016/j.yexcr.2025.114709","DOIUrl":"10.1016/j.yexcr.2025.114709","url":null,"abstract":"<div><h3>Background</h3><div>As a core pathological process of cardiovascular disease, atherosclerosis (AS) progression is closely linked to macrophage polarization, yet the mechanisms by which post-translational modifications regulate inflammatory responses in AS remain unclear.</div></div><div><h3>Methods</h3><div>Using oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 foam macrophages and high-fat diet-fed (apolipoprotein E knockout) ApoE^−/− mice, we assessed HMGN2 SUMOylation's role in macrophage M2 polarization. Cell proliferation/migration were analyzed via EdU/Transwell assays; macrophage polarization phenotypes were examined by immunofluorescence. Inflammatory cytokines and NF-κB pathway were quantified using ELISA/Western blot. Aortic plaque formation and lipid deposition were evaluated through HE staining and Oil Red O lipid visualization.</div></div><div><h3>Results</h3><div>In cellular experiments, research demonstrated that HMGN2 enhances interaction with the transcription factor PAX5 through SUMOylation, thereby inhibiting PAX5 activity and driving macrophage polarization toward the pro-inflammatory M1 phenotype. Furthermore, PIAS1 knockdown significantly reduced HMGN2 SUMOylation levels. This disruption suppressed the binding between PAX5 and HMGN2 and reduced inflammatory factor release. Animal experiments revealed that targeted PIAS1 knockdown markedly reduced aortic plaque area, improved lipid metabolic disorders, and modulated inflammatory cytokines by inhibiting NF-κB signaling pathway.</div></div><div><h3>Conclusion</h3><div>The present study systematically reveals the molecular mechanism by which HMGN2 SUMOylation regulates macrophage polarization and inflammatory response through the \"PAX5-NF-κB\" signaling axis, which may become a new target for the treatment of atherosclerosis by targeting epigenetic modification.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114709"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887092","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 “Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling” [Exp. Cell. Res. 364(2) (2018)198–207]","authors":"Shaobo Tian ,&nbsp;Jia Hu ,&nbsp;Kaixiong Tao ,&nbsp;Jian Wang ,&nbsp;Yanan Chu ,&nbsp;Jing Li ,&nbsp;Zhibo Liu ,&nbsp;Xueliang Ding ,&nbsp;Luming Xu ,&nbsp;Qilin Li ,&nbsp;Ming Cai ,&nbsp;Jinbo Gao ,&nbsp;Xiaoming Shuai ,&nbsp;Guobin Wang ,&nbsp;Lin Wang ,&nbsp;Zheng Wang","doi":"10.1016/j.yexcr.2025.114655","DOIUrl":"10.1016/j.yexcr.2025.114655","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114655"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505274","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":"Membrane attack complex impairs hepatocyte autophagy in alcohol-related liver disease by regulating the SIRT1-FOXO3 signaling","authors":"Zhigao Hu ,&nbsp;Shanshan Jiang ,&nbsp;Zhen Wan ,&nbsp;Laihui Luo ,&nbsp;Minglong Wang ,&nbsp;Hua Qiu ,&nbsp;Yanqiang Wang ,&nbsp;Yu Liu ,&nbsp;Renfeng Shan","doi":"10.1016/j.yexcr.2025.114713","DOIUrl":"10.1016/j.yexcr.2025.114713","url":null,"abstract":"<div><h3>Background</h3><div>Impaired hepatocyte autophagy is a key feature of alcohol-related liver disease (ALD). Activation of the membrane attack complex (MAC) regulates autophagy. This study examined the role and regulatory mechanisms of MAC in hepatocyte autophagy during ALD progression.</div></div><div><h3>Methods</h3><div>For the animal model, C57BL/6 mice were fed a Lieber-DeCarli liquid diet containing 5 % ethanol (EtOH) (w/v). For the cell model, AML12 cells were exposed to 100 mM EtOH for 72 h. Pathological changes in the liver were examined using hematoxylin–eosin staining, and hepatic steatosis was evaluated using Oil Red O staining. The mRNA and protein expression levels were analyzed by RT-qPCR and western blotting, respectively. Secretion levels of pro-inflammatory cytokines were determined by ELISA. Immunofluorescence staining was employed to detect C5b-9 and LC3 levels, as well as FOXO3 cellular localization. The interaction between FOXO3 and the LAMP2 promoter was analyzed using the ChIP assay.</div></div><div><h3>Results</h3><div>MAC inhibition reduced liver injury, lipid accumulation, and inflammation in the liver tissues of ALD mice while promoting hepatocyte autophagy. CD59 overexpression not only inhibited EtOH-induced lipid accumulation and inflammation in AML12 cells but also promoted autophagy by activating the SIRT1-FOXO3 axis. Mechanistically, SIRT1 promoted FOXO3-mediated LAMP2 transcriptional activation by enhancing the deacetylation and nuclear translocation of FOXO3. As expected, SIRT1 silencing weakened the effects of CD59 overexpression on lipid accumulation, inflammatory response, and autophagy in EtOH-treated AML12 cells.</div></div><div><h3>Conclusion</h3><div>MAC inhibition enhances LAMP2-mediated hepatocyte autophagy in ALD by promoting SIRT1-mediated FOXO3 deacetylation and nuclear translocation, thereby alleviating ALD progression.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114713"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895463","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":"Antagonistic interaction between Notch3 signaling and CREB/KLF15 pathway in regulating the phenotypic alterations of glomerular parietal epithelial cells in adriamycin-induced nephropathy","authors":"Yuqing Zhu ,&nbsp;Kaili Chang ,&nbsp;Ke Sun ,&nbsp;Yifeng Wang ,&nbsp;Zhonghua Zhao ,&nbsp;Qi Chen ,&nbsp;Qiaojing Qin ,&nbsp;Xueguang Liu","doi":"10.1016/j.yexcr.2025.114724","DOIUrl":"10.1016/j.yexcr.2025.114724","url":null,"abstract":"<div><div>Parietal epithelial cells (PECs) that line the Bowman’s capsule are considered progenitor cells for podocytes, which exhibit limited regeneration capacity following injury. Notch3 receptor has been found to be co-expressed in both podocytes and PECs in focal segmental glomerulosclerosis (FSGS), suggesting a distinct regulatory role in this context. Our previous research indicated that Notch3 signaling is significantly negatively correlated with the cAMP-PKA-CREB-KLF15 pathway in adriamycin (ADR)-injured podocytes. Given the common embryonic origin of PECs and podocytes, we hypothesize that Notch3 signaling and CREB-KLF15 pathway may play a critical role in the phenotypic alterations of PECs. We generated Notch3 knockout mice and established ADR-induced nephropathy. Notably, Notch3 knockdown improved both renal function and morphology in middle-aged mice (56–60 weeks) and those with ADR-induced nephropathy. In Notch3^+/− mice, the number of PECs co-expressing podocyte markers was significantly higher compared to that in wild-type mice. In cultured PECs, ADR directly induced phenotypic changes of PECs by modulating Notch3 signaling and CREB-KLF15 pathway. Notch3 overexpression by lentiviral transfection resulted in significant activation of PECs and increased expressions of p-ERK. Furthermore, pCPT-cAMP, a selective activator of cAMP-PKA pathway, or VRAD medium, markedly enhanced CREB-KLF15 pathway and the expressions of podocyte markers. U0126, a specific inhibitor of MEK/ERK, significantly inhibited Notch3 signaling while concurrently increasing the expression of CREB-KLF15. Taken together, these findings suggest that Notch3-p-ERK signaling and CREB-KLF15 pathway exert antagonistic effects in modulating PECs phenotype, with p-ERK potentially serving as a molecular switch in the interaction between these two signaling pathways.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114724"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904177","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":"Retraction notice to “Silenced long non-coding RNA activated by DNA damage elevates microRNA-495-3p to suppress atherosclerotic plaque formation via reducing Krüppel-like factor 5” [Exp. Cell Res. 401 (2021) 112519]","authors":"Dan-Ni Fu ,&nbsp;Yu Wang ,&nbsp;Li-Jun Yu ,&nbsp;Ming-Jie Liu ,&nbsp;Dong Zhen","doi":"10.1016/j.yexcr.2025.114633","DOIUrl":"10.1016/j.yexcr.2025.114633","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114633"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274550","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 ‘Analysis of the in vitro response of the Sapajus cay (Primates: Platyrrhini) genome to exposure to the radiomimetic bleomycin’ [Exp. Cell Res. 450 (2025) 114689]","authors":"Mariela Nieves ,&nbsp;Romina Celeste Páez ,&nbsp;Esteban Orlando Ferreras ,&nbsp;Melina Noelia Ortuño Orgaz ,&nbsp;Nancy Beatriz Andrioli","doi":"10.1016/j.yexcr.2025.114698","DOIUrl":"10.1016/j.yexcr.2025.114698","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114698"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855004","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":"Inhibition of crosstalk between iNKT cells and macrophages mitigates ischemia-reperfusion injury in steatotic livers","authors":"Yu Kuroda ,&nbsp;Yoshiya Ito ,&nbsp;Nobuyuki Nishizawa ,&nbsp;Mina Tanabe ,&nbsp;Atsushi Yamashita ,&nbsp;Kanako Hosono ,&nbsp;Mariko Kamata ,&nbsp;Masashi Satoh ,&nbsp;Yusuke Kumamoto ,&nbsp;Naoki Hiki ,&nbsp;Hideki Amano","doi":"10.1016/j.yexcr.2025.114728","DOIUrl":"10.1016/j.yexcr.2025.114728","url":null,"abstract":"<div><div>Liver ischemia-reperfusion (IR) injury is a substantial form of damage that occurs during liver transplantation and resection surgeries. Steatotic livers are particularly susceptible to IR injury, but few strategies to effectively alleviate this issue in steatotic livers exist. Invariant natural killer T (iNKT) cells regulate IR injury in healthy livers as well as liver repair by interacting with macrophages. In this study, we explored the role of iNKT cell-macrophage crosstalk in IR injury in steatotic livers. High-fat diet (HFD)-fed macrophage-specific CD1d conditional knockout (<em>Cd1d</em>^{<em>△mac</em>}) and Cd1d^flox control (Cont) mice were subjected to liver IR. HFD-fed <em>CD1d</em>^{<em>△mac</em>} mice showed mitigation of IR-induced liver damages with reduction of hepatic necrosis and inflammation along with promotion of liver repair. Flow cytometric analysis revealed that HFD-fed <em>Cd1d</em>^{<em>△mac</em>} mice showed increased hepatic reparative macrophages and interleukin (IL)-13-positive iNKT cells but decreased pro-inflammatory macrophages with IL-1β. IL-13 administration to HFD-fed Cont mice attenuated IR injury and accelerated liver recovery, which was associated with accumulation of hepatic macrophages skewed to a reparative phenotype. IL-13 promoted reparative macrophage polarization in bone marrow (BM)-derived <em>Cd1d</em>-deficient macrophages in vitro. Blockade of IL-13 in HFD-fed <em>Cd1d</em>^{<em>△mac</em>} mice aggravated IR injury. Overall, inhibiting iNKT cell-macrophage crosstalk attenuates steatotic liver IR injury and facilitates liver repair via IL-13-mediated reparative macrophage polarization. These findings provide new insights into therapeutic strategies to regulate the vulnerability of the steatotic liver to IR injury.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114728"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916355","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":"Retraction notice to “DDX18 influences chemotherapy sensitivity in colorectal cancer by regulating genomic stability” [Exp. Cell Res. 444 (2025) 114344]","authors":"Wenchao Zhao ,&nbsp;Qingqing Luo ,&nbsp;Han Zhan ,&nbsp;Zhen Du ,&nbsp;Tan Deng ,&nbsp;Huaxin Duan","doi":"10.1016/j.yexcr.2025.114559","DOIUrl":"10.1016/j.yexcr.2025.114559","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114559"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274549","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}