Cellular signalling最新文献

{"title":"USP7-DDX5-FASN axis drives fatty acid metabolism and supports hepatocellular carcinoma progression","authors":"Jiawei Wang ,&nbsp;Lihua Zhou ,&nbsp;Yujia Pan ,&nbsp;Cai Li ,&nbsp;Shuxian Huang ,&nbsp;Zhaofang Yan ,&nbsp;Haipeng Wang ,&nbsp;Guangying Qi ,&nbsp;Jinfeng Gan","doi":"10.1016/j.cellsig.2025.111947","DOIUrl":"10.1016/j.cellsig.2025.111947","url":null,"abstract":"<div><div>Lipid metabolism plays a critical role in meeting the biosynthetic demands of rapidly proliferating tumor cells and is a major driver in the development of hepatocellular carcinoma (HCC). However, the precise molecular mechanisms underlying this process remain unclear. In this study, we identified DEAD box protein 5 (DDX5) as a key regulator of fatty acid synthesis in HCC. Analysis of multiple HCC cohorts revealed a marked elevation in DDX5 expression, which is closely correlated with poorer clinical outcomes. Functional studies demonstrated that DDX5 facilitates HCC cell proliferation, enhances colony formation, and promotes fatty acid synthesis through the upregulation of fatty acid synthetase (FASN). In vivo studies showed that inhibition of DDX5 effectively suppressed tumor growth. Further investigation identified an interaction between DDX5 and ubiquitin-specific peptidase 7 (USP7), whereby USP7 stabilizes DDX5 by removing ubiquitin chains through deubiquitination. Collectively, these findings highlight the USP7-DDX5-FASN axis as a critical regulator of fatty acid metabolism in HCC progression, offering potential avenues for therapeutic intervention.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111947"},"PeriodicalIF":4.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330898","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":"Activation of STING pathway by mitochondrial fission negatively regulates adipogenic differentiation of 3 T3-L1 cells","authors":"Kai Ma ,&nbsp;Haoxuan Sun ,&nbsp;Xiaoyun Wu ,&nbsp;Jinping Quan ,&nbsp;Rong Tang ,&nbsp;Weiwei Liu ,&nbsp;Toshihiko Hayashi ,&nbsp;Kazunori Mizuno ,&nbsp;Shunji Hattori ,&nbsp;Hitomi Fujisaki ,&nbsp;Takashi Ikejima","doi":"10.1016/j.cellsig.2025.111948","DOIUrl":"10.1016/j.cellsig.2025.111948","url":null,"abstract":"<div><div>Adipocyte hyperplasia refers to the increase in the number of adipocytes, whereas adipocyte hypertrophy pertains to the enlargement of individual adipocytes resulting from the accumulation of lipid droplets. In this study, we found that activation of the STING signalling pathway occurs during adipogenic differentiation of 3 T3-L1 preadipocytes. Interestingly, inhibiting the STING pathway by using STING antagonist H151 or siRNA targeting STING promotes adipocyte differentiation and increases adipocyte numbers, while activation of STING inhibits adipogenic differentiation. Silencing the STING canonical downstream IRF3, or inhibiting the proton channel activity of STING enhances adipogenic differentiation, confirming the negative modulation of adipogenic differentiation by STING. <em>In vivo</em>, intraperitoneal injection of H151 into mice with a high-fat diet further enhances the adipocyte hyperplasia, as shown by the increased volume of adipose tissues, but consistent sizes of adipocytes. During the adipogenic differentiation of 3 T3-L1 cells, DRP1-mediated mitochondrial fission is enhanced, and causes mitochondrial DNA leakage, which in turn activates the STING pathway. However, inhibition of mitochondrial fission represses adipogenic differentiation of 3 T3-L1 cells in spite of the down-regulation of STING pathway. Therefore, our results indicate that adipogenic differentiation is associated with DRP1-induced mitochondrial fission. However, the leakage of mitochondrial DNA caused by DRP1-induced mitochondrial fission activates the STING signalling pathway, which negatively regulates adipogenic differentiation. Tissue specific reduction of DRP1-associated mitochondrial fission or STING enhancement might be new strategies for the therapy of obesity-associated diseases.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111948"},"PeriodicalIF":4.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324550","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":"TNALP promotes epithelial oxidative stress and fibrosis via SIRT3-dependent mechanisms in tracheal injury","authors":"Zhiqiang Liu ,&nbsp;Hailang Peng ,&nbsp;Mingyu Peng ,&nbsp;Jiaxin Liao ,&nbsp;Bin Liu ,&nbsp;Rongjuan Zhuang ,&nbsp;Hongwei Yang ,&nbsp;Li Xu ,&nbsp;Yishi Li ,&nbsp;Lei Gao ,&nbsp;Shuliang Guo","doi":"10.1016/j.cellsig.2025.111943","DOIUrl":"10.1016/j.cellsig.2025.111943","url":null,"abstract":"<div><div>Benign tracheal stenosis (BTS) remains a clinical challenge due to high postoperative restenosis rates and the absence of effective pharmacological treatments. Although fibrosis has traditionally been attributed to fibroblast activation, epithelial injury is increasingly recognized as an early initiating event. This study identified tissue-nonspecific alkaline phosphatase (TNALP) as a key mediator of epithelial damage and fibrotic progression in BTS. Analyses of patient specimens, animal models, and cultured epithelial cells revealed that TNALP suppressed SIRT3 expression level, a mitochondrial deacetylase that can regulate oxidative stress and apoptosis. Pharmacological inhibition of TNALP with tetramisole restored SIRT3 expression level, attenuated oxidative damage, reduced epithelial cell death, and mitigated tissue fibrosis. These preclinical findings highlight TNALP as a potential therapeutic target and support further investigation into the repurposing of TNALP inhibitors as antifibrotic agents to reduce restenosis following tracheal surgery.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111943"},"PeriodicalIF":4.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307675","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":"miRNA-548d-3p represses non-small cell lung cancer growth by perturbing DDX5-mediated pyroptosis through JAK2/STAT3 signaling","authors":"Liyu Liu ,&nbsp;Qinglin Liu ,&nbsp;Zhining Wu ,&nbsp;Jiao Wu ,&nbsp;Xiaoyan Chen ,&nbsp;Bocheng Zhang ,&nbsp;Xiao Pang ,&nbsp;Shixuan Liang ,&nbsp;Ying Long ,&nbsp;Ying Liu","doi":"10.1016/j.cellsig.2025.111945","DOIUrl":"10.1016/j.cellsig.2025.111945","url":null,"abstract":"<div><h3>Background</h3><div>The function of microRNAs (miRNAs) in tumor development has been extensively characterized. Pyroptosis is a kind of programmed death, which can effectively hinder cancer development. However, there is still a large gap in the function of miRNAs in NSCLC pyroptosis.</div></div><div><h3>Methods</h3><div>The pyroptosis-related differentially expressed miRNAs and their promising targets in NSCLC were analyzed using bioinformatic analyses. The effects of miR-548d-3p on cell proliferation, pyroptosis and tumor growth were verified in vivo and in vitro. The expression of pyroptosis-related factors was examined in cells and xenografted tumors. Additionally, the molecular interaction was assessed by using Co-IP and dual-luciferase reporter gene assays.</div></div><div><h3>Results</h3><div>We found that miR-548d-3p was poorly expressed in NSCLC in public datasets and an independent cohort of 48 NSCLC patients. Low miR-548d-3p expression was positively associated with pathologic T stage and poor prognosis of NSCLC patients. Transfection of miR-548d-3p mimics significantly decreased the cell viability of NSCLC cells, partly attributing to the increase in the proportion of pyroptotic cells. These changes were accompanied by a rise in the protein abundance of NLRP3, ASC, cleaved Caspase-1 and GSDMD-N and release of IL-1β and IL-18. Integrating bioinformatic, expressional and experimental analyses, we predicted and validated DDX5 as the direct target of miR-548d-3p. Furthermore, we demonstrated that miR-548d-3p/DDX5 axis regulated pyroptosis via the Phosphorylated JAK2/STAT3-mediated NLRP3/Caspase-1/GSDMD pathway in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>Our study revealed that miR-548d-3p/DDX5 promoted pyroptosis in NSCLC by promoting the JAK2/STAT3/NLRP3/Caspase-1/GSDMD pathway, indicating the promising effect of miR-548d-3p in NSCLC treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111945"},"PeriodicalIF":4.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315997","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":"Identification of lactylation-related hub genes as novel therapeutic and diagnostic targets for thoracic aortic dissection","authors":"Jinxing Peng ,&nbsp;Zhuohang Jiang ,&nbsp;Jiayu Song ,&nbsp;Jinze Chen ,&nbsp;Ziyun Fu ,&nbsp;Huizhe Zhang ,&nbsp;Jianfan Zhen ,&nbsp;Muhetaijiang Tuerdi ,&nbsp;Mingyang Luo ,&nbsp;Jinlin Wu ,&nbsp;Tucheng Sun","doi":"10.1016/j.cellsig.2025.111944","DOIUrl":"10.1016/j.cellsig.2025.111944","url":null,"abstract":"<div><h3>Background</h3><div>Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease with high mortality rates. Although lactylation has garnered increasing attention, its role in TAD remains poorly understood.</div></div><div><h3>Methods</h3><div>Lactylation-related genes (LRGs) were obtained from the MsigDB database. Lactylation-related hub genes (LRHGs) were identified by intersecting LRGs with differentially expressed genes and WGCNA results. Lactylation was assessed in a β-aminopropionitrile (BAPN)-induced mouse model and human aortic tissues. Two single-cell RNA sequencing (scRNA-seq) from the GEO database were utilized to evaluate lactylation patterns across cell populations and intercellular communication networks. Biomarkers were evaluated using receiver operating characteristic (ROC) analysis.</div></div><div><h3>Results</h3><div>Elevated lactylation levels were observed in both TAD tissues and synthetic phenotype vascular smooth muscle cells. Through integrated analysis, we identified 12 LRHGs, which includes LDHA. In the BAPN-induced mouse model, LDHA inhibitors (Oxamate and FX11) significantly reduced mortality rates and decreased aortic lactate levels and protein lactylation. ScRNA-seq analytic results revealed that monocytes and macrophages exhibited the highest lactylation activity, which likely enhanced their inflammatory pathways and intercellular communication. ROC analysis showed the lowest AUC of 12 LRHGs is 0.8893.</div></div><div><h3>Conclusions</h3><div>This study highlights the critical role of lactylation-related hub genes in TAD, identifying potential therapeutic targets and diagnostic biomarkers, which provides novel insights into the molecular mechanisms underlying TAD.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111944"},"PeriodicalIF":4.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315981","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":"Corrigendum to “O-GlcNAcylated c-Jun antagonizes ferroptosis via inhibiting GSH synthesis in liver cancer” [Cellular Signalling, 2019 Nov:63:109384. doi:10.1016/j.cellsig.2019.109384]","authors":"Yan Chen ,&nbsp;Guoqing Zhu ,&nbsp;Ya Liu ,&nbsp;Qi Wu ,&nbsp;Xiao Zhang ,&nbsp;Zhixuan Bian ,&nbsp;Yue Zhang ,&nbsp;Qiuhui Pan ,&nbsp;Fenyong Sun","doi":"10.1016/j.cellsig.2025.111915","DOIUrl":"10.1016/j.cellsig.2025.111915","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111915"},"PeriodicalIF":4.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301204","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":"Overexpression of Rap1B alleviate central precocious puberty and neurodevelopmental damage","authors":"Xiaodong Liu ,&nbsp;Lingwen Zeng","doi":"10.1016/j.cellsig.2025.111941","DOIUrl":"10.1016/j.cellsig.2025.111941","url":null,"abstract":"<div><h3>Introduction</h3><div>The central precocious puberty (CPP) in children and adolescents can adversely impact their overall well-being, affecting both their physical and psychological health. Whether Rap1B can mitigate the development of CPP remains unknown.</div></div><div><h3>Methods</h3><div>The expression of Rap1B was investigated through a comprehensive bioinformatics analysis. Precocious puberty model in rats was established through high-fat feeding (HFD), and further injected AAV-Rap1B. Then, HE staining, vaginal exfoliated cell smear and other methods were used to explore the incidence of precocious puberty in rats in each group. In addition, Western blot, RT-qPCR, and IHC was used to detect the expression of GnRH, GnRHR, Kiss1, Kiss1R, NeuN, BDNF, TH, AVP. The contents of LH, FSH, E2, T, and AMH in serum of rats were detected by ELISA. The Rap1B cell line was constructed at the cellular level to explore the effects of FFA(OA + PA) induction on cell proliferation, apoptosis and inflammation.</div></div><div><h3>Results</h3><div>The expression of Rap1B was significantly up-regulated in overexpressing MKRN3 cells, where overexpressing MKRN3 can alleviate the occurrence of CPP. Overexpression of Rap1B alleviates HFD-induced CPP models, including reduce the content of LH, FSH, E2, T, and AMH in serum, and inhibit the expression of GnRH, Kiss1 and Kiss1R in hypothalamus, and alleviates hypothalamus injury. Furthermore, overexpression of Rap1B in the GT1–7 cell. Overexpression of Rap1B can significantly reverse FFA damage to GT1–7 cells and reduce FFA-induced increase of inflammatory factors (IL-6, IL-1β and TNF-α) in GT1–7 cells.</div></div><div><h3>Conclusion</h3><div>This study indicated that overexpression of Rap1B alleviate CPP and neurodevelopmental damage. Our study offers a new approach for the treatment of CPP.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111941"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301205","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":"Roflumilast inhibits neuronal ferroptosis via AMPK/Nrf2/HO-1 signaling and promotes motor function recovery after spinal cord injury in rats","authors":"YaoNan Han,&nbsp;XingTong Wang,&nbsp;DeShui Yu","doi":"10.1016/j.cellsig.2025.111930","DOIUrl":"10.1016/j.cellsig.2025.111930","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a serious central nervous system disease. Ferroptosis is one of the major causes of spinal cord neurological loss, and targeting ferroptosis is a promising therapeutic strategy. Roflumilast has shown promising applications in the treatment of neurological diseases due to its potent anti-inflammatory and anti-oxidative stress effects. This study aimed to investigate whether roflumilast could inhibit neuronal ferroptosis to improve motor function after SCI in rats. In vitro experiments, we found that roflumilast significantly increased cell survival in an in vitro ferroptosis model, improved mitochondrial function, reduced intracellular iron, reactive oxygen species (ROS), and lipid peroxides accumulation as well as the expression of the pro-ferroptosis proteins, long-chain acyl-coenzyme A synthase 4 (ACSL4), and prostaglandin-endoperoxide synthase 2 (PTGS2), and increased the expression of ferroptosis-inhibitory protein glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) expression. Mechanistically, these protective effects were achieved by activating AMP-dependent protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and were attenuated when AMPK signaling was blocked. In vivo experiments, roflumilast attenuated spinal cord tissue damage, increased the number of motor neuron survivors, and improved motor function after SCI in rats. Overall, activation of AMPK/Nrf2/HO-1 signaling by roflumilast attenuated neuronal ferroptosis and improved motor function after SCI in rats.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111930"},"PeriodicalIF":4.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280798","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":"PPP1CA promotes hepatocellular carcinoma progression in a YAP1-dependent way","authors":"Xing Liu ,&nbsp;Guangxi Xu ,&nbsp;Weiming Luo ,&nbsp;Kaisheng Wang ,&nbsp;Feitong Wang","doi":"10.1016/j.cellsig.2025.111938","DOIUrl":"10.1016/j.cellsig.2025.111938","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) exhibits high incidence, malignancy, and mortality rates. Inactivation of the Hippo pathway has been implicated in the acquisition of malignant characteristics in HCC. The present study identifies upregulation of protein phosphatase 1 catalytic subunit alpha (PPP1CA) in HCC tissues, with elevated PPP1CA expression correlating with poor prognosis in patients with HCC. Functionally, PPP1CA acts as an oncogenic driver that facilitates cell proliferation and migration in HCC. Mechanistic investigations reveal that PPP1CA interacts with YAP1, inducing YAP1 dephosphorylation and promoting its nuclear translocation, ultimately activating transcription of Hippo pathway target oncogenes. Additionally, PPP1CA knockdown exhibits a synergistic effect with YAP1 inhibitors, significantly suppressing HCC tumor proliferation <em>in vivo</em>. Collectively, these findings underscore the pivotal role of PPP1CA in regulating HCC tumorigenesis through a YAP-dependent mechanism, highlighting PPP1CA as a promising therapeutic target for HCC intervention.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111938"},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288787","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":"ENY2 promotes hepatocellular carcinoma progression via CSN5-mediated regulation of HDAC11 and FOXO1 signaling","authors":"Ben Niu ,&nbsp;Tao Li ,&nbsp;Chunqi Xie ,&nbsp;Fanjun Meng ,&nbsp;Yan Yang ,&nbsp;Hongting Diao ,&nbsp;Jing Ji ,&nbsp;Yuxiang Fei","doi":"10.1016/j.cellsig.2025.111937","DOIUrl":"10.1016/j.cellsig.2025.111937","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"134 ","pages":"Article 111937"},"PeriodicalIF":4.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293406","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}