Cellular signalling最新文献

{"title":"Significant roles of RNA 5-methylcytosine methylation in cancer.","authors":"Na Lou, Xinyu Gu, Leiya Fu, Juan Li, Chen Xue","doi":"10.1016/j.cellsig.2024.111529","DOIUrl":"10.1016/j.cellsig.2024.111529","url":null,"abstract":"<p><p>Cancer stands as a leading cause of mortality and poses an escalating threat to global health. Epigenetic dysregulation is pivotal in the onset and advancement of cancer. Recent research on RNA 5-methylcytosine (m⁵C) methylation has underscored its significant role in cancer. RNA m⁵C methylation is a key component in gene expression regulation and is intricately linked to cancer development, offering valuable insights for cancer diagnosis, treatment, and prognosis. This review provides an in-depth examination of the three types of regulators associated with RNA m⁵C methylation and their biological functions. It further investigates the expression and impact of RNA m⁵C methylation and its regulators in cancer, focusing on their mechanisms in cancer progression and clinical relevance. The current research on inhibitors targeting RNA m⁵C methylation-related regulators remains underdeveloped, necessitating further exploration and discovery.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111529"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766621","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":"Game-changing breakthroughs to redefine the landscape of the renin-angiotensin-aldosterone system in health and disease.","authors":"Pitchai Balakumar, Gowraganahalli Jagadeesh","doi":"10.1016/j.cellsig.2024.111459","DOIUrl":"10.1016/j.cellsig.2024.111459","url":null,"abstract":"<p><p>Novel perspectives on the role of the renin-angiotensin-aldosterone system (RAAS) offer a groundbreaking understanding of the system's role in health and illness. Our understanding of the role of the RAAS in several diseases, such as heart failure, hypertension, metabolic disorders, and chronic renal disease, has been broadened by recent studies. Specific variations in RAAS pathways can affect the course of disease and response to treatment, as shown by genetic and molecular research. The dynamic and fast-evolving nature of RAAS research described in this special issue might transform our approach to managing renal, neurological, and cardiovascular health, among other disease conditions, including cancer.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111459"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399550","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":"Fusion circRNA F-circEA1 facilitates EML4-ALK1 positive lung adenocarcinoma progression through the miR-4673/SMAD4/ADAR1 axis.","authors":"Yinping Huo, Dongmei Yuan, Hongbing Liu, Yong Song","doi":"10.1016/j.cellsig.2024.111571","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111571","url":null,"abstract":"<p><p>Circular RNA (circRNA) can sponge miRNA participate in the tumorigenesis and progression of various cancers. We substantiate for the first time that the fusion circular RNA (F-circRNA) F-circEA1 is involved in driving the echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase variant 1-positive (EML4-ALK1) lung adenocarcinoma (LUAD) progression and the expression of the parental gene EML4-ALK1, molecular mechanisms of F-circEA1 in the EML4-ALK1 LUAD remain unknown. Bioinformatics analysis showed that only miR-4673 can bind to F-circEA1 and bind to EML4-ALK1 3'-UTR to regulate the expression of EML4-ALK1. Notably, high miR-4673 expression exerted an inhibitory impact on the invasion, migration, and proliferation of EML4-ALK1-positive LUAD cells, and partially reversed the invasion, migration, and proliferation of F-cirEA1. F-circEA1 can sponge miR-4673, enhanced the recombinant mothers against decapentaplegic homolog 4 (SMAD4) expression, which is a downstream target of miR-4673. As a transcription factor, SMAD4 exhibits the ability to directly associate with EML4-ALK1 and adenosinedeaminase RNA editingenzyme 1 (ADAR1) promoter regions. Interestingly, it was also observed that the RNA editing enzyme ADAR1 facilitated the expression of F-circEA1, but inhibited the expression of miR-4673. The interplay between F-circEA1, miR-4673, SMAD4, and ADAR1 forms a feedback pathway that aids in regulating the progression of EML4-ALK variant 1-positive LUAD. This novel finding offers promising therapeutic ideas for the EML4-ALK variant 1-positive lung adenocarcinoma.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111571"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876260","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":"Tumor cells induce neural DKK1 expression to promote MDSC infiltration and subsequent T cell suppression.","authors":"Ruoyan Liu, Xiaotian Shi, Shuangshuang Qian, Zhonghao Sun, Hao Dai, Yongwei Wu, Shihui Cao, Jingtao Luo, Ze Zhang","doi":"10.1016/j.cellsig.2024.111576","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111576","url":null,"abstract":"<p><p>Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions. Based on these findings, we hypothesize that tumors may induce DKK1 expression in nerves, and that nerve-derived DKK1 may promote MDSC infiltration and immunosuppression. To test this hypothesis, we employed a combination of experimental approaches, including in vitro co-culture of trigeminal ganglia with tumor cells, multiplex immunohistochemistry, and in vivo administration of DKK1 neutralizing antibodies. Our results indicate that tumor cells significantly induce DKK1 expression in ganglia in co-culture experiments. Additionally, in vivo orthotopic tumor models revealed that DKK1 levels were markedly elevated in both the plasma and ganglia of tumor-bearing mice. Neutralization DKK1 in vivo led to a reduction in MDSC levels and impaired MDSC-mediated T cell suppression in both HNSCC and PDAC orthotopic models. Furthermore, conditional deletion of neuronal DKK1 elucidated its role in MDSC infiltration and immune suppression. Our findings establish a novel molecular axis in which tumor cells modulate the immune microenvironment by inducing the expression of secreted proteins in nerves, thereby enriching the research landscape of the tumor microenvironment.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111576"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876267","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":"Wnt5a alleviates the symptoms of PCOS by modulating PI3K/AKT/mTOR pathway-mediated autophagy in granulosa cells.","authors":"Yabo Ma, Yuqin Ma, Pengfei Li, Fucheng Ma, Miao Yu, Jinrui Xu, Yi Yang","doi":"10.1016/j.cellsig.2024.111575","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111575","url":null,"abstract":"<p><strong>Objective: </strong>Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disease that entails dysregulated ovulation, hyperandrogenism, and polycystic ovaries. While Wnt5a has been suggested to play key roles in follicular development and female fertility under normal conditions, its functions in the context of PCOS have yet to be established. This study was thus designed to explore the impact of Wnt5a on ovarian granulosa cell autophagy in PCOS, providing in vitro evidence in support of its role in this setting.</p><p><strong>Methods: </strong>DHT-induced granulosa (KGN) cells were used as an in vitro model, and Wnt5a and autophagy-related protein levels in these cells were detected via Western blotting. Downregulating the expression of Wnt5a in KGN cells (by interference and inhibitor) was also performed, and Western blotting, RT-PCR, and immunofluorescence strategies were used to detect autophagy-related and PI3K/AKT/mTOR pathway-associated factors in this setting. In vivo, BOX5 was tested as a therapeutic inhibitor of Wnt5a in a murine model of DHEA-induced PCOS. Changes in ovarian morphology were detected through hematoxylin staining, while E2 and T hormone levels were quantified by ELISA, and autophagy-related factors in these animals were quantified through Western blotting, immunofluorescence, and immunohistochemistry.</p><p><strong>Results: </strong>Wnt5a and autophagy-related protein levels rose significantly in DHT-induced KGN cells. Following downregulation of the Wnt5a in these cells, a significant decrease in autophagy-related factor levels was noted relative to the DHT group, together with significant increases in pathway-related factors. In mice, BOX5 treatment was sufficient to restore serum levels of androgen and to improve polycystic ovarian changes, while also suppressing the levels of autophagy-associated factors within ovarian granulosa cells.</p><p><strong>Conclusion: </strong>Wnt5a downregulation suppresses autophagy in PCOS granulosa cells through the activation of the PI3K/AKT/mTOR pathway, in addition to remediating polycystic ovarian changes and normalizing serum levels of sex hormones.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111575"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876272","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":"Mechanism underlying CDC20 affecting epithelial ovarian cancer biological behavior by regulating BAG6 ubiquitination.","authors":"Xiaocui Zhang, Fangfang Bi, Qing Yang","doi":"10.1016/j.cellsig.2024.111577","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111577","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC) endangers women's life and health. It is reported that cell division cycle 20 (CDC20) plays a role in EOC, but its underlying mechanisms remain unclear. Additionally, the involvement of bcl-2-associated athanogen-6 (BAG6) in EOC has not been previously reported. This study demonstrated that CDC20 was highly expressed in EOC and exhibited oncogenic properties through both in vitro and in vivo molecular biology experiments. In contrast, BAG6 was low expressed and functioned as a tumor suppressor. Both CDC20 and BAG6 were found to correlate with patient stage. Notably, the degradation of BAG6, mediated by CDC20 via ubiquitin-proteasome pathway, was shown to enhance the malignant biological behavior of EOC. Furthermore, the interaction between CDC20 and BAG6 was dependent on the WD40 domain of CDC20 and the D-box of BAG6. These findings provided valuable insights into the molecular mechanisms of EOC and established a theoretical basis for novel therapeutic targets in clinical treatment.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111577"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876263","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":"ALKBH5 promotes cardiac fibroblasts pyroptosis after myocardial infarction through Notch1/NLRP3 pathway.","authors":"Liu-Gen Cui, Shu-Hui Wang, Sumra Komal, Jian-Jian Yin, Miao-Miao Zhai, Yue-Jiao Zhou, Qing-Wen Yu, Cong Wang, Pei Wang, Zhi-Mo Wang, Aliza Muhammad Zafar, Muhammad Shakeel, Li-Rong Zhang, Sheng-Na Han","doi":"10.1016/j.cellsig.2024.111574","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111574","url":null,"abstract":"<p><p>Through bioinformatics screening, we previously found that AlkB homolog 5 (ALKBH5) expression, an m⁶A demethylase, was higher in patients with heart failure than in the normal population. This study aimed to investigate the molecular mechanisms by which ALKBH5 regulates heart failure. We established a myocardial infarction (MI)-induced heart failure model in rats in vivo and an in vitro hypoxia model using rat primary cardiac fibroblasts (RCFs). M⁶A sequencing, RNA immunoprecipitation assay, RNA pull-down assay, proximity ligation assay, gain-of-function and loss-of-function experiments, and transcriptomic analysis were performed to confirm the pyroptosis-promoting effects of ALKBH5. The effects of two small-molecule inhibitors (ZINC78774792 and ZINC00546946) on ALKBH5 expression were examined. The expression of m⁶A demethyltransferase ALKBH5 was significantly elevated in hypoxia-induced RCFs. Transcriptional profiling revealed Notch receptor 1 (Notch1) as an m⁶A modification target of ALKBH5, and Notch1 mRNA m⁶A modifications were increased in ALKBH5-deficient RCFs. Moreover, Notch1 and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) are associated. ALKBH5 knockdown alleviated hypoxia-induced RCF cell pyroptosis by inhibiting Notch1, NLRP3 inflammasome activation, and pyroptosis-associated protein (N-GSDMD), whereas ALKBH5 overexpression had the opposite effect. Targeting ALKBH5 with two small-molecule inhibitors (ZINC78774792 and ZINC00546946) reduced hypoxia-induced RCF pyroptosis, and ZINC00546946 alleviated cell pyroptosis after myocardial infarction in mice. Our results indicate that ALKBH5 promotes cardiac fibroblast pyroptosis after myocardial infarction through the Notch1/NLRP3 pathway. Therefore, inhibiting ALKBH5 may be a strategy for treating cardiovascular diseases.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111574"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876256","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":"METTL3-mediated m6A modifications of NLRP3 accelerate alveolar bone resorption through enhancing macrophage pyroptosis.","authors":"Qiudong Yang, Junhong Xiao, Yuqi Liu, Zhengkun Yang, Chuan Wang, Jiahui Sun, Huiyi Wang, Heyu Liu, Xiaoxuan Wang, Li Ma, Xin Huang, Zhengguo Cao","doi":"10.1016/j.cellsig.2024.111572","DOIUrl":"10.1016/j.cellsig.2024.111572","url":null,"abstract":"<p><p>Periodontitis (PD) is twice as prevalent in diabetics compared to nondiabetics, and diabetes-associated PD is characterized by increased inflammation and aggravated tissue damage. Pyroptosis has recently been implicated in diabetes-associated PD; however, the underlying mechanisms remain largely unknown, resulting in a lack of effective treatments. In this study, we investigated the role of methyltransferase-like 3 (METTL3) in macrophage pyroptosis and found that it inhibits the osteogenic differentiation of osteoblasts via pyroptotic macrophages in a diabetes-associated periodontitis mouse model. Further analysis and validation revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) is a target of METTL3, with its mRNA stability regulated through a binding of insulin-like growth factor 2 binding protein 3 (IGF2BP3)-dependent pathway. Additionally, local injection of adeno-associated virus 9 (AAV9) demonstrated that METTL3 deficiency in macrophages significantly ameliorates periodontal inflammation and alveolar bone loss in diabetes-associated PD mice. Collectively, our findings indicate that METTL3-mediated modulation of NLRP3 expression is a crucial factor in macrophage pyroptosis during diabetes-associated PD progression. This suggests that the METTL3/IGF2BP3/NLRP3 axis is a novel and promising target for the improvement of periodental inflammation and alveolar bone loss in diabetes-associated PD.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111572"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871614","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 AXL as a novel positive regulator of lipid raft in gastric cancer.","authors":"Zhi Yang, Chuanfu Ren, Ziyun He, Banxin Luo, Xin Chen, En Xu, Wenxian Guan, Xuefeng Xia","doi":"10.1016/j.cellsig.2024.111573","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111573","url":null,"abstract":"<p><p>Lipid rafts are highly heterogeneous and dynamic microdomains involved in molecule trafficking and signaling transduction. This study investigates the role of lipid rafts in gastric cancer and their key regulators. Analyzing FFPE samples from 111 gastric cancer patients, we found that high lipid raft levels predict poor prognosis. Modulating these levels in gastric cancer cell lines significantly impacted cell proliferation, migration, and invasion. Weighted Gene Co-expression Network Analysis identified AXL as a hub gene associated with lipid rafts. AXL knockdown experiments revealed its interaction with Caveolin-1, a caveolae lipid raft protein, which regulates lipid raft levels and promotes AKT and ERK signaling, enhancing cancer development and metastasis. In vivo tumorigenesis assays and survival analyses further supported these findings. This study underscores the significance of lipid rafts in gastric cancer and identifies AXL as a novel regulator, offering new insights into the molecular mechanisms of cancer progression and suggesting potential therapeutic targets.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111573"},"PeriodicalIF":4.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871601","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 \"Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD1\" [Cellular Signalling, 28: (2016) 412-424].","authors":"Ailsa Watson, Christopher Lipina, Harry J McArdle, Peter M Taylor, Harinder S Hundal","doi":"10.1016/j.cellsig.2024.111567","DOIUrl":"https://doi.org/10.1016/j.cellsig.2024.111567","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111567"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853220","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}