Cellular signalling最新文献

{"title":"RBM39 silence suppresses esophageal cancer proliferation and metastasis via FANCD2 mRNA destabilization.","authors":"Xin Yang, Chunyang Li, Chu Zhang, Liwen Zhang, Wei Wei, Mei Ji, Bo Jiang","doi":"10.1016/j.cellsig.2025.112047","DOIUrl":"10.1016/j.cellsig.2025.112047","url":null,"abstract":"<p><p>Esophageal cancer (ESCA) is a lethal malignancy with limited therapeutic options and poor survival outcomes. Here, we identify RBM39 as a novel oncoprotein that drives ESCA progression through post-transcriptional stabilization of Fanconi anemia, complementation group D2 (FANCD2) mRNA. RNA-binding motif protein 39 (RBM39) is significantly upregulated in ESCA tissues and cell lines, and its high expression correlates with poor overall survival (OS) and disease-free survival (DFS) in clinical cohorts. Functional studies demonstrate that RBM39 knockdown suppresses proliferation, migration, and invasion in ESCA cells (TE-1, TE-12) in vitro and impairs tumor growth and pulmonary metastasis in xenograft models. Mechanistically, RBM39 directly binds the 3' untranslated regions (3'-UTR) of FANCD2 mRNA (validated by RIP-qPCR and motif mutagenesis), extending its half-life (actinomycin D assay). ESCA transcriptomic profiling of TCGA database links RBM39 to the Fanconi anemia DNA repair pathway, with FANCD2 as its top target. Critically, FANCD2 overexpression rescues oncogenic phenotypes upon RBM39 silencing, restoring tumorigenesis in vivo. These findings establish the RBM39-FANCD2 axis as a therapeutic vulnerability, where targeting the RBM39-FANCD2 axis may offer a promising therapeutic strategy for the ESCA clinical treatment.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112047"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768465","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":"ACSS3 protein macromolecule regulates glycolysis in keloid through Wnt/β-catenin signaling pathway: Bioinformatics, machine learning, and experimental validation.","authors":"Pingping Huo, Sujie Wang, Zhouna Li, Zhehu Jin","doi":"10.1016/j.cellsig.2025.112056","DOIUrl":"10.1016/j.cellsig.2025.112056","url":null,"abstract":"<p><p>Keloids are fibroproliferative lesions resulting from abnormal wound healing, characterized by the excessive growth and metabolic reprogramming of keloid fibroblasts (KFs). The underlying mechanisms responsible for these metabolic abnormalities remain under debate. This research employed comprehensive bioinformatics techniques to pinpoint ACSS3 (Acetyl-CoA Synthetase Short-Chain Family Member 3) and the Wnt/β-Catenin pathway as pivotal contributors to keloid pathogenesis. ACSS3, a mitochondrial protein involved in metabolic regulation, is downregulated in keloid. Lentiviral transfection-induced overexpression of ACSS3 suppressed KFs activity, normalized glycolytic flux, and reduced the levels of critical glycolytic enzymes. Conversely, ACSS3 knockdown elicited opposite effects, which were reversed by ICG-001. Single-cell analysis demonstrates that fibroblasts are the primary cell type involved in the fibrotic process. An ACSS3 regulatory network was developed. Additionally, Molecular docking and dynamics simulations were conducted to identify potential drugs targeting ACSS3. In summary, this study demonstrates that ACSS3 modulates aerobic glycolysis and the activity of KFs via the Wnt/β-Catenin pathway, positioning ACSS3 as a promising therapeutic target for keloid treatment.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112056"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811861","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":"ALDH2 inhibits angiogenesis in esophageal squamous cell carcinoma by suppressing the NOTCH1/PI3K/Akt signaling pathway.","authors":"Jingchao Qiang, Tian Qiu, Yongliang Yang, Baoshi Xu, Hongyu Huang, Xinran Li, Rui Ma, Yingzhi Lu, Zibo Dong","doi":"10.1016/j.cellsig.2025.112025","DOIUrl":"10.1016/j.cellsig.2025.112025","url":null,"abstract":"<p><p>Esophageal Squamous Cell Carcinoma (ESCC) stands as the predominant form of esophageal cancer globally, bearing high morbidity and mortality rates attributed to its capacity for infiltration and metastasis. Angiogenesis emerges as a pivotal factor influencing ESCC progression. To explore how to modulate angiogenesis for anti-ESCC therapy effectively, here we evaluated the potential of acetaldehyde dehydrogenase 2 (ALDH2) as a targeted therapy for ESCC and elucidated the molecular mechanisms by which ALDH2 inhibits ESCC angiogenesis. Our findings reveal a correlation between low ALDH2 expression and the progression as well as poor prognosis of ESCC. Additionally, ESCC cell apoptosis was stimulated while ESCC cell proliferation, migration, invasion, and angiogenesis were all successfully suppressed by ALDH2 overexpression. Regarding the molecular mechanism, ALDH2 was observed to suppress NOTCH1, which in turn inhibited the PI3K/Akt pathway, thereby hindering the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA), which are both linked to angiogenesis, and ultimately exerting its inhibitory effect on ESCC through this regulatory cascade. Importantly, we established a subcutaneous xenograft tumor model in BALB/c nude mice using ESCC cell lines with ALDH2 overexpression. Our results demonstrated that ALDH2 overexpression significantly inhibited tumor growth and angiogenesis, further supporting ALDH2 as a potential therapeutic target in ESCC. Finally, we screened Tectoridin (TEC), an agonist of ALDH2, and demonstrated its ability to inhibit ESCC. These findings provide an empirical basis for the development of novel therapeutic strategies for ESCC.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112025"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741342","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":"Post-translational modifications of Stat3: The state of the art.","authors":"Jiaxu Chen, Caiyun Mao, Ning Han, Qi Zhou, Chenhao Feng, Xutao Sun, Yunjia Song","doi":"10.1016/j.cellsig.2025.112048","DOIUrl":"10.1016/j.cellsig.2025.112048","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 3 (Stat3), a critical transcription factor, plays an essential role in cellular processes such as proliferation, development, and differentiation. It also significantly contributes to the pathogenesis of cardiovascular diseases and various cancers, including breast cancer, pancreatic cancer, and renal cell carcinoma. The functional dynamics of Stat3 are intricately regulated by post-translational modifications (PTMs) such as phosphorylation, sulfenylation, acetylation, sulfhydrylation, and SUMOylation. These modifications, triggered by pathophysiological signals, induce structural changes in Stat3 across different cell types, thereby regulating distinct gene expression programs. Such modifications can either enhance or inhibit Stat3's transcriptional activity and affect its DNA-binding stability. This review explores the various PTMs that modulate Stat3 function, offering a comprehensive analysis of the regulatory mechanisms that govern Stat3 within cellular signaling networks. The findings are expected to provide valuable insights into the development of novel therapeutic agents targeting these pathways, ultimately revealing new targets and innovative strategies for treating a range of diseases.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112048"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793526","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":"TRIM10β upregulation promotes microtubule destabilization and triggers proteotoxic stress.","authors":"Heesoo Kim, Wonji Shin, Byunghoon Jeon, Sungwook Lee, Boyoun Park","doi":"10.1016/j.cellsig.2025.112052","DOIUrl":"10.1016/j.cellsig.2025.112052","url":null,"abstract":"<p><p>Microtubule stability is critical for maintaining cytoskeletal integrity and is finely tuned by post-translational modifications of tubulin and its associated regulatory factors. However, it remains unclear how microtubules become destabilized under stress or disease conditions and contribute to pathogenesis. Here, we identify TRIM10β, a previously uncharacterized splice variant of TRIM10, as a microtubule-associated protein that disrupts the interaction between tubulin and End Binding protein 1 (EB1), which plays a critical role in microtubule stabilization. Moreover, TRIM10β promotes tubulin SUMOylation and cleavage of LIM domain kinase 1 (LIMK1), both of which contribute to microtubule destabilization. TRIM10β binds to calmodulin-regulated spectrin-associated protein 2 (CAMSAP2), a key regulator of non-centrosomal microtubules, and modulates its protein levels via its E3 ligase activity. Notably, TRIM10β depletion attenuates p38 phosphorylation in erythroblasts, which is essential for microtubule disassembly and polarization during enucleation, whereas its ectopic expression aberrantly enhances p38 activity, promoting microtubule disassembly in non-erythroid cells. Importantly, persistent overexpression of TRIM10β is recognized as a proteotoxic burden and rapidly degraded via the unfolded protein response (UPR) under cellular stress, thereby serving as a protective mechanism. Our findings reveal a novel role for TRIM10β in microtubule dynamics and highlight a potential regulatory mechanism in maintaining proteostasis, with its low endogenous expression possibly reflecting an evolutionary strategy to minimize proteostatic stress.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112052"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803680","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":"Kindlin-1 promotes mitophagy by inhibiting PINK1 degradation to enhance hepatocellular carcinoma progression and modulates sensitivity to donafenib.","authors":"Huaxing Ma, Guangling Ou, Bibo Wu, Hongwei Ding, Yijie Zhang, Fei Xia, Zixuan Shen, Kunyang Zhao, Chaochun Chen, Long Wu, Jin Lei, Yuan Xu, Xueke Zhao, Kun Cao, Haiyang Li","doi":"10.1016/j.cellsig.2025.112032","DOIUrl":"10.1016/j.cellsig.2025.112032","url":null,"abstract":"<p><p>Mitophagy, essential for mitochondrial homeostasis, may affect hepatocellular carcinoma (HCC) progression and drug sensitivity, though its precise role remains unclear. Kindlin-1 is an adhesion protein which can regulate the function of integrins, resulting in an aggressive phenotype in certain solid malignant tumors.This study explored the clinical significance and cellular functions of Kindlin-1 in HCC. The role of Kindlin-1 in HCC progression was assessed, along with its effects on mitophagy and sensitivity to donafenib. Its impact on HCC cell proliferation and metastasis was analyzed using CCK8, colony formation, EdU incorporation, flow cytometry, Immunohistochemistry, Transwell assays, wound healing assays, and subcutaneous tumorigenesis in nude mice. The interactions of Kindlin-1 with other proteins and its main functions and pathways were investigated through RNA sequencing, enrichment analysis, immunohistochemical co-localization, Co-IP and mass spectrometry. Additionally, the effects of Kindlin-1 on PINK1 stability and mitophagy were evaluated, and the impact of Kindlin-1 inhibition on donafenib sensitivity was tested in vitro and in vivo. Kindlin-1 was found to be highly expressed in HCC tissues and correlated with a poor prognosis. Kindlin-1 promotes mitophagy by stabilizing full-length PINK1 and prevents ubiquitin induced degradation of PINK1 by interacting with it, thus promoting HCC cell proliferation. Inhibition of Kindlin-1 expression or mitophagy synergistically enhances the anti-tumor effects of donafenib in vitro and in xenograft mouse models. Our study demonstrates that Kindlin-1 significantly influences HCC progression by regulating mitophagy through the PINK1/Parkin pathway. Inhibiting Kindlin-1 may represent a promising therapeutic strategy to enhance the efficacy of donafenib, thereby providing novel insights into improving treatment outcomes for HCC patients.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112032"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759294","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":"CPSF6 loss mediates LDHA 3'UTR shortening to promote fibroblast glycolysis and pulmonary fibrosis.","authors":"Huanyu Yang, Mengjia Han, Li Zhang, Changhong Yao, Qi Xu","doi":"10.1016/j.cellsig.2025.112165","DOIUrl":"10.1016/j.cellsig.2025.112165","url":null,"abstract":"<p><p>Pulmonary fibrosis is a chronic and progressive fibrotic lung disease with a poor prognosis and few treatment options. Alternative polyadenylation (APA), an important post-transcriptional regulatory mechanism, remains poorly understood in pulmonary fibrosis. In this study, we found that cleavage and polyadenylation-specific factor 6 (CPSF6), a key regulator of APA, was downregulated in silica-induced mouse fibrotic lung tissue. AAV-mediated in vivo overexpression of CPSF6 could mitigate the progression of pulmonary fibrosis induced by silica. Moreover, CPSF6 knockdown in fibroblasts enhanced fibroblast (MRC-5 cell line and mouse primary lung fibroblast) activation and glycolytic activity. ONT-RNA-seq data and subsequent experiments indicated that CPSF6 loss favored the utilization of the proximal poly (A) site in the 3' untranslated region (UTR) of lactate dehydrogenase (LDHA), resulting in a short-3'UTR LDHA isoform that produced more protein due to avoiding miR-4317 targeting. The upregulation of LDHA mediated the profibrotic effect of CPSF6 loss by facilitating glycolysis and contributed to the transition of fibroblasts into myofibroblasts. Taken together, our findings indicate that the CPSF6 silence promotes fibroblast glycolysis and pulmonary fibrosis progression by upregulating LDHA expression through the loss of miR-4317-mediated repression resulting from alternative polyadenylation of the LDHA mRNA 3' UTR. CPSF6 and its downstream effector may represent promising targets for pulmonary fibrosis treatment.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112165"},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273895","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":"Adipose-derived mesenchymal stem cell exosomes protect keratinocytes from high-glucose injury by modulating KEAP1/NRF2/HO-1 axis.","authors":"Yixuan Yuan, Shijie Song, Yujie Xiao, Rongqin Feng, Mengyang Li, Hao Zhang, Liang Luo, Kejia Wang, Peng Wang, Lai Wei, Yihao Zhang, Boxing Zhang, Shiqing Jiang, Kuo Shen, Hao Guan, Dahai Hu","doi":"10.1016/j.cellsig.2025.112172","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.112172","url":null,"abstract":"<p><p>Hyperglycemia exacerbates diabetic chronic wounds by inducing oxidative damage and epithelial-mesenchymal transition (EMT), impairing re-epithelialization. This study investigated the protective role of adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) against high glucose (HG)-induced keratinocyte injury and diabetic wound healing impairment. ADSC-Exos were isolated via density gradient ultracentrifugation, characterized using NTA, TEM, and immunoblotting, and applied to HG-treated HaCaT cells and diabetic mouse wounds. In vitro, ADSC-Exos significantly mitigated HG-induced oxidative stress by reducing reactive oxygen species (ROS), DNA damage (8-OHdG), and lipid peroxidation (MDA), while enhancing antioxidant enzymes (SOD, CAT). Mechanistically, ADSC-Exos suppressed KEAP1, activated the NRF2/HO-1 pathway, and attenuated pathological EMT-like changes by restoring E-cadherin and suppressing N-cadherin, α-SMA, and Vimentin. In diabetic mice, ADSC-Exos accelerated wound closure, improved collagen deposition, and reduced inflammatory cytokines (IL-1β, IL-6, TNF-α). These findings demonstrate that ADSC-Exos promote diabetic wound healing by alleviating oxidative stress and pathological EMT-like changes via KEAP1/NRF2/HO-1 signaling, supporting their potential as a therapeutic strategy for diabetic chronic wounds.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112172"},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307050","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":"Advances in cardiac cell interaction studies: Implications for heart disease treatment.","authors":"Liang Huang, Bingbing Xie, Andy Peng Xiang, Qiuling Xiang","doi":"10.1016/j.cellsig.2025.112161","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.112161","url":null,"abstract":"<p><p>Heart disease remains a leading cause of significant health threats, posing substantial risks to global public health. However, owing to the incomplete understanding of the mechanisms underlying cell-cell interactions within the heart, effective clinical interventions and treatments remain limited. The heart is a cellularly heterogeneous organ comprising multiple cell types, such as cardiomyocytes, endothelial cells, cardiac fibroblasts, macrophages, lymphocytes and pericytes. Interactions among these cell types play a critical role in cardiac injury and repair processes. In this review, we discuss the latest advancements in the study of cellular interactions within the heart, integrating findings from cellular models, animal studies, and organoid research. We highlight the roles of specific cell types during cardiac injury and repair. Additionally, we also discuss potential therapeutic strategies for injured hearts based on insights gained from cell interaction studies. In summary, understanding the mechanisms of cell-cell interactions offers promise for developing targeted therapeutic strategies.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112161"},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307116","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":"MiR-383-3p attenuates sepsis-induced myocardial ferroptosis by targeting ATF4 and inhibiting the ATF4-CHOP-CHAC1 signaling axis.","authors":"Yazhou Li, Yan Shao, Jie Su, Shimin Dong","doi":"10.1016/j.cellsig.2025.112169","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.112169","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role and mechanism of miR-383-3p in sepsis-induced myocardial dysfunction (SIMD), with a focus on ferroptosis.</p><p><strong>Methods: </strong>Plasma miR-383-3p levels were measured in sepsis patients with/without SIMD and healthy controls. In vitro, LPS-treated rat cardiomyocytes (H9C2) were transfected with miR-383-3p mimics or inhibitors. Ferroptosis was modulated using erastin or ferrostatin-1. Target prediction and dual-luciferase assays identified ATF4 as a miR-383-3p target. Key markers were assessed by qRT-PCR, Western blot, ELISA, and flow cytometry. In vivo, a murine sepsis model received miR-383-3p agomir; cardiac function and ferroptosis markers were evaluated.</p><p><strong>Results: </strong>Plasma miR-383-3p was significantly downregulated in SIMD patients, correlating negatively with injury markers (cTnI, CK-MB) and disease severity (SOFA, APACHE II), and positively with cardiac function (LVEF, LVFS). LPS downregulated miR-383-3p and induced ferroptosis/injury in H9C2 cells, which miR-383-3p overexpression mitigated. miR-383-3p directly targeted ATF4 mRNA, suppressing the ATF4-CHOP-CHAC1 axis, reducing lipid peroxidation (lower Fe²⁺, ROS, MDA,LDH; higher GSH), and downregulating pro-ferroptotic genes (ACSL4). Furthermore, overexpression of ATF4 abolished the protective effects of miR-383-3p, while knockdown of ATF4 phenocopied the suppressive effects of miR-383-3p on the CHOP-CHAC1 axis and ferroptosis. In vivo, miR-383-3p agomir improved cardiac function, reduced inflammation/injury markers, attenuated mitochondrial damage, and inhibited the ATF4-CHOP-CHAC1 pathway in LPS-treated mice.</p><p><strong>Conclusion: </strong>This study identifies a novel mechanism whereby miR-383-3p attenuates SIMD by targeting ATF4 and inhibiting the ATF4-CHOP-CHAC1 signaling axis, thereby suppressing cardiomyocyte ferroptosis. Therefore, our study demonstrates for the first time that the downregulation of miR-383-3p exacerbates SIMD by activating the ATF4-CHOP-CHAC1-mediated ferroptosis pathway.Our findings represents a potential therapeutic target for sepsis-induced cardiac injury.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"112169"},"PeriodicalIF":3.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298983","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}