Cellular signalling最新文献

{"title":"New insights into prostate Cancer from the renin-angiotensin-aldosterone system.","authors":"Yashvi Patel ,&nbsp;Payal Thapa ,&nbsp;Akhilesh Prajapati","doi":"10.1016/j.cellsig.2024.111442","DOIUrl":"10.1016/j.cellsig.2024.111442","url":null,"abstract":"<div><div>Prostate cancer is among the most common malignancies found in men, with multifactorial changes occurring altogether to disrupt the pathophysiology of this gland. The Renin-Angiotensin-Aldosterone System (RAAS) is an extensively studied pathway that has newly attributed fundamental roles in cancer biology that impact cell growth, migration, metastasis, and death. These processes are significantly influenced by various components of the RAAS, including prorenin, AT1R, AT2R, and Ang 1–7/Mas receptors. Although the pathophysiology of prostate cancer is complex, targeting the RAAS shows promise as a therapeutic approach. RAAS dysregulation is evident in prostate cancer, and treatments traditionally used for cardiovascular diseases are being explored for cancer therapy. The RAAS pathway has significant effects on the formation of new blood vessels (angiogenesis), the spread of cancer cells to other parts of the body (metastasis), and cell proliferation. In this pathway, angiotensin II and its receptors have crucial functions. Angiotensin II stimulates angiogenesis and cell proliferation through the AT1R, whereas the AT2R has the opposite effect by inhibiting cell growth. Additional pathways involving ACE2/Ang 1–7/Mas also provide potential targets for therapeutic intervention, mitigating the impact of the traditional ACE/Angiotensin II/AT1R pathway. The components of the RAAS influence multiple signalling pathways, such as Androgen Receptor (AR), NF-κB, and PI3K/AKT/mTOR, which enhances our understanding of how it contributes to the progression of prostate cancer. This also provides new possibilities for therapeutic interventions.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111442"},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379066","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":"ZFHX2-AS1 interacts with DKC1 to regulate ARHGAP5 pseudouridylation and suppress ovarian cancer progression","authors":"Yongshun Dong ,&nbsp;Zili Zhang ,&nbsp;Hongmei Huang ,&nbsp;Yonghui Yu ,&nbsp;Boqi Rao ,&nbsp;Xinjie Kuang ,&nbsp;Jie Zeng ,&nbsp;Eryong Zhao ,&nbsp;Yongxiu Chen ,&nbsp;Jiachun Lu ,&nbsp;Fuman Qiu","doi":"10.1016/j.cellsig.2024.111441","DOIUrl":"10.1016/j.cellsig.2024.111441","url":null,"abstract":"<div><div>Ovarian cancer (OCa) remains a highly lethal disease, largely due to late-stage diagnosis and limited treatment options for recurrent metastatic tumors. Long non-coding RNAs (lncRNAs) have been recognized as key regulators of cancer hallmarks, yet their specific roles in driving OCa progression are not fully understood. In this study, we employed an integrated approach combining clinical correlation, functional assays, and mechanistic investigations to reveal that lncRNA ZFHX2-AS1 is significantly downregulated in OCa tissues and cells, with its reduced expression associated with poor clinical outcomes. Using in vitro and in vivo models, we demonstrated that overexpression of ZFHX2-AS1 suppresses OCa cell proliferation, migration and invasion, whereas ZFHX2-AS1 knockdown enhances these malignant phenotypes. Mechanistically, we defined that ZFHX2-AS1 interacts with and attenuates the enzymatic activity of the pseudouridine synthase DKC1, thereby reducing pseudouridylation and stabilizing the oncogenic ARHGAP5 mRNA. <em>Re</em>-expression of ARHGAP5 could partially reverse the tumor-suppressive effects of ZFHX2-AS1. Further, we found that ARHGAP5 promotes epithelial-mesenchymal transition (EMT) by regulating Rho GTPases activities, and that ZFHX2-AS1 inhibits EMT in OCa by downregulating ARHGAP5 expression and suppressing the Rho GTPase signaling pathway. Taken together, our findings identify ZFHX2-AS1 as a potent tumor suppressor in OCa, acting through the modulation of DKC1-mediated pseudouridylation of ARHGAP5 and the inhibition of the Rho GTPase pathway, thus offering a potential therapeutic target for combating OCa progression.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111441"},"PeriodicalIF":4.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379069","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":"Non-cyclic nucleotide EPAC1 activators suppress lipopolysaccharide-regulated gene expression, signalling and intracellular communication in differentiated macrophage-like THP-1 cells","authors":"Jolanta Wiejak ,&nbsp;Fiona A. Murphy ,&nbsp;Graeme Barker ,&nbsp;Pasquale Maffia ,&nbsp;Stephen J. Yarwood","doi":"10.1016/j.cellsig.2024.111444","DOIUrl":"10.1016/j.cellsig.2024.111444","url":null,"abstract":"<div><div>This study explores the anti-inflammatory effects of non-cyclic nucleotide EPAC1 activators, PW0577 and SY007, on lipopolysaccharide (LPS)-induced responses in differentiated THP-1 macrophage-like cells. Both activators were found to selectively activate EPAC1 in THP-1 macrophages, leading to the activation of the key down-stream effector, Rap1. RNA sequencing analysis of LPS-stimulated THP-1 macrophages, revealed that treatment with PW0577 or SY007 significantly modulates gene expression related to fibrosis and inflammation, including the suppression of NLRP3, IL-1β, and caspase 1 protein expression in LPS-stimulated cells. Notably, these effects were independent of p65 NFκB phosphorylation at Serine 536, indicating a distinct mechanism of action. The study further identified a shared influence of both activators on LPS signalling pathways, particularly impacting extracellular matrix (ECM) components and NFκB-regulated genes. Additionally, in a co-culture model involving THP-1 macrophages, vascular smooth muscle cells, and human coronary artery endothelial cells, EPAC1 activators modulated immune-vascular interactions, suggesting a broader role in regulating cellular communication between macrophages and endothelial cells. These findings enhance our understanding of EPAC1's role in inflammation and propose EPAC1 activators as potential therapeutic agents for treating inflammatory and fibrotic conditions through targeted modulation of Rap1 and associated signalling pathways.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111444"},"PeriodicalIF":4.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HNRNPD/MAD2L2 axis facilitates lung adenocarcinoma progression and is a potential prognostic biomarker","authors":"Zhuoyu Gu ,&nbsp;Weizheng Ding ,&nbsp;Shuang Yuan ,&nbsp;Youqiang Peng ,&nbsp;Bo Dong ,&nbsp;Yike Gu ,&nbsp;Jing Li ,&nbsp;Yitong Chen ,&nbsp;Kailu Wang ,&nbsp;Tianze Liu ,&nbsp;Xiaodan Han ,&nbsp;Yixin Li","doi":"10.1016/j.cellsig.2024.111443","DOIUrl":"10.1016/j.cellsig.2024.111443","url":null,"abstract":"<div><h3>Background</h3><div>Although progress has been made in the treatment of LAUD, the survival rate for patients remains poor. An in-depth grasp of the molecular pathways implicated in LUAD progression is vital for improving diagnosis and treatment strategies. This study aims to explore novel molecular mechanisms driving LUAD progression and identify new potential prognostic biomarkers for LAUD patients.</div></div><div><h3>Methods</h3><div>Based on mass spectrometry analysis of human LUAD tissues, HNRNPD and MAD2L2 were identified as potential key proteins involved in LUAD progression. Subsequently, the interplay between HNRNPD and MAD2L2 was examined through dual-luciferase reporter assays, RNA-seq analysis, and various molecular biology techniques. Ultimately, the role of the HNRNPD/MAD2L2 axis in LUAD advancement and its potential as a prognostic indicator were investigated utilizing LUAD specimens, cell lines, and xenograft mouse models.</div></div><div><h3>Results</h3><div>In human LAUD tissues and cell lines, elevated levels of HNRNPD and MAD2L2 proteins were discovered. It was determined that HNRNPD binds to the MAD2L2 promoter, forming a regulatory axis at the transcriptional level. Subsequently, both <em>in vitro</em> and <em>in vivo</em> data demonstrated that the downregulation of the HNRNPD/MAD2L2 axis inhibited LUAD progression, while this effect could be rescued by MAD2L2 upregulation. Conversely, the upregulation of the HNRNPD/MAD2L2 axis facilitated LUAD progression, and this outcome could be reversed by MAD2L2 knockdown. Mechanistically, the downregulation of HNRNPD suppressed the promoter activity and transcription of MAD2L2, thus inhibiting the PI3K/HIF1α/ANGPTL4 pathway and tumor angiogenesis. Finally, it was confirmed that LUAD patients with high levels of both HNRNPD and MAD2L2 exhibited the poorest prognosis. Therefore, the HNRNPD/MAD2L2 axis has been identified as a potential predictive indicator for LUAD patients.</div></div><div><h3>Conclusions</h3><div>The HNRNPD/MAD2L2 axis facilitates LUAD progression and serves as a potential prognostic biomarker.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111443"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNRPB2 in the pan-cancer landscape: A bioinformatics exploration and validation in hepatocellular carcinoma","authors":"Bowen Li ,&nbsp;Jiang Liu ,&nbsp;Ling Huang ,&nbsp;Jing Cai ,&nbsp;Liangyun Guo ,&nbsp;Liangzhi Xu ,&nbsp;Qi Xu ,&nbsp;Jinghang Liu ,&nbsp;Jian Huang ,&nbsp;Wei Hu ,&nbsp;Xinguo Tang ,&nbsp;Zhaohui Liu ,&nbsp;Tiande Liu","doi":"10.1016/j.cellsig.2024.111445","DOIUrl":"10.1016/j.cellsig.2024.111445","url":null,"abstract":"<div><div>Aberrant splicing is a significant contributor to gene expression abnormalities in cancer. SNRPB2, a component of U2 small nuclear ribonucleoprotein particles (snRNPs), contributes to the assembly of the spliceosome, the molecular machinery responsible for splicing. To date, few studies have investigated the role of SNRPB2 in tumorigenesis. We examined data sourced from various public databases, such as The Cancer Genome Atlas(TCGA), the Clinical Proteomic Tumor Analysis Consortium(CPTAC), and Gene Expression Omnibus(GEO). Our investigation included gene expression, genomic and epigenomic scrutiny, gene set enrichment assessment(GSEA), and immune cell infiltration evaluation. Furthermore, we performed empirical validation to ascertain the impact of SNRPB2 suppression on the proliferation and migration of liver cancer cells. Analysis of gene expression revealed widespread upregulation of SNRPB2 across a spectrum of cancer types, with heightened levels of SNRPB2 expression in numerous tumors linked to unfavorable prognosis. Genomic and epigenomic assessments revealed connections between SNRPB2 expression and variations in SNRPB2 copy number, DNA methylation patterns, and RNA modifications. Through gene set enrichment analysis, the involvement of SNRPB2 in vital biological processes and pathways related to cancer was identified. Furthermore, scrutiny of immune cell infiltration suggested a potential relationship between SNRPB2 and the tumor microenvironment, which was reinforced by multiple single-cell sequencing profiles. Subsequent experimental validation revealed that silencing SNRPB2 effectively impeded the proliferation and migration of liver cancer cells. Taken together, these findings underscore the prospective utility of SNRPB2 as a prognostic biomarker and a promising candidate for immunotherapy in cancer. It is necessary to engage in additional exploration into its underlying mechanisms and clinical treatment potential.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111445"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375218","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":"Single-cell analysis reveals that TCF7L2 facilitates the progression of ccRCC via tumor-associated macrophages","authors":"Fengran Guo ,&nbsp;Yilong Gao ,&nbsp;Pengfei Zhou ,&nbsp;Hu Wang ,&nbsp;Ziyang Ma ,&nbsp;Xiaowei Wang ,&nbsp;Xin Wang ,&nbsp;Xiaojuan Feng ,&nbsp;Yaxuan Wang ,&nbsp;Zhenwei Han","doi":"10.1016/j.cellsig.2024.111453","DOIUrl":"10.1016/j.cellsig.2024.111453","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-associated macrophages (TAMs) play an important role in the recurrence and progression of clear cell renal cell carcinoma (ccRCC). However, the specified mechanism has not been elucidated.</div></div><div><h3>Methods</h3><div>Single-cell and transcriptome analysis were applied to characterize the heterogeneity of TAMs. SCENIC would infer regulators of different subsets of TAMs. The CellChat algorithm was used to infer macrophage-tumor interaction networks, whereas pseudo-time traces were used to parse cell evolution and dynamics.</div></div><div><h3>Results</h3><div>In this study, single-cell transcriptomic data of ccRCC were analyzed. Notably, the macrophages were clustered to select the cluster with a tendency toward M2-type TAM, which has an impact on the occurrence and metastasis of ccRCC. This macrophage cluster was defined as “TAM2”. And this study revealed that TCF7L2 as a potential transcription factor regulating TAM2 transcriptional heterogeneity and differentiation. Pseudotime traces showed TCF7L2 trajectories during TAM2 cell cluster development. In addition, the results of cell interaction showed that TAM2 had the highest number and strength of interactions with cancer cells and endothelial cells. <em>In vitro</em> experiments, this study found that TCF7L2 was highly expressed in TAMs and promoted the polarization of macrophages to M2-type macrophages. And then overexpression of TCF7L2 in macrophages markedly promoted ccRCC invasion and proliferation.</div></div><div><h3>Conclusion</h3><div>TCF7L2 could play a key role in the progression of ccRCC <em>via</em> enhancing TAMs recruitment and M2-type polarization.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111453"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of DT-13 regulating macrophages in diabetic wound healing","authors":"Li Kun ,&nbsp;Diao Yunpeng ,&nbsp;Fan Shuyuan","doi":"10.1016/j.cellsig.2024.111446","DOIUrl":"10.1016/j.cellsig.2024.111446","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Diabetes is a complex metabolic system disease, and one of the main reasons why it is difficult to heal is that macrophages cannot realize the transition from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. &lt;em&gt;Liriope spicata&lt;/em&gt; Lour. is a traditional Chinese medicine. According to the theory of traditional Chinese medicine, &lt;em&gt;Liriope spicata&lt;/em&gt; Lour. has nourishing Yin Sheng Jin, moistening lung clear heart, used for lung dryness dry cough, Yin deficiency cough, throat arthralgia throat pain, thirst, internal heat thirst, upset insomnia, intestinal dryness constipation, is the classification of Yin tonifying drugs. &lt;em&gt;Liriope muscari&lt;/em&gt; baily saponins C (DT-13) is one of the main active ingredients of &lt;em&gt;Liriope spicata&lt;/em&gt; Lour., has significant anti-inflammatory, anti-tumor, and immunomodulatory effects.&lt;/div&gt;&lt;div&gt;This thesis aims to explore the role of DT-13 in angiogenesis by regulating the polarization of macrophages, and ultimately play an anti-inflammatory role in regeneration by regulating immune cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted in vivo experiments using a diabetic mouse ulcer model to verify the effect of DT-13 in promoting wound healing. Spatial transcriptome sequencing technology was utilized to perform RNA transcript analysis on wound tissues from type II diabetic mice and non-diabetic mice. Subsequently, we used the CCK-8 assay to evaluate the impact of DT-13 on the viability of THP-1 cells (human monocytes). ELISA, immunofluorescence, and Western blot techniques were employed to study the mechanisms by which DT-13 inhibits the sustained inflammation and polarization process of M1 macrophages induced by LPS. The Transwell assay was used to assess the influence of DT-13 treatment on the co-culture of M1 macrophages induced by LPS under high glucose conditions with HUVEC cells. Finally, the chick embryo chorioallantoic membrane (CAM) assay was applied to explore the effects of DT-13 on angiogenesis stimulated by M1 macrophages under high glucose conditions with LPS stimulation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We found that DT-13 can promote wound healing in a diabetic ulcer model in mice. Through spatial transcriptome sequencing results, we discovered that type II diabetic mice had higher levels of inflammation at the wound site and abnormal expression of macrophage characteristic proteins. The CCK-8 assay detected that DT-13 at 20 μmol/L had an effect on THP-1 cells. Through Q-PCR, ELISA, immunofluorescence, and Western blot results, we found that the mechanism by which DT-13 exerts anti-inflammatory effects on M1 macrophages with sustained inflammation induced by LPS under high glucose conditions may be through the TLR4-NFKB signaling pathway, and the mechanism for inducing the polarization of M1 macrophages to M2 type may be through the ERK-STAT3 signaling pathway. Interestingly, through the Transwell assay, we found that M1 macrophages induced b","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111446"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375216","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":"Bone marrow mesenchymal stem cells-derived exosomal miR-381 alleviates lung ischemia-reperfusion injury by activating Treg differentiation through inhibiting YTHDF1 expression","authors":"Cao Gao ,&nbsp;Lei Chen ,&nbsp;Xiang-yu Xie ,&nbsp;Xiao-feng He ,&nbsp;Jiang Shen ,&nbsp;Liang Zheng","doi":"10.1016/j.cellsig.2024.111440","DOIUrl":"10.1016/j.cellsig.2024.111440","url":null,"abstract":"<div><h3>Aim</h3><div>Our study aimed to investigate whether BMSCs-derived exosomal miR-381 promotes Treg cell differentiation in lung ischemia-reperfusion injury (LIRI), and the underlying mechanism.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> and <em>in vivo</em> models of LIRI were established by hypoxia/reoxygenation (H/R) treatment and lung ischemia/reperfusion (I/R) surgery, respectively. BMSCs-derived exosomes were isolated and identified by western blot, nanoparticle tracking analysis, and transmission electron microscopy. Cell viability, proliferation, and apoptosis were assessed by CCK-8, EdU, and flow cytometry assay, respectively. IL-18 secretion level in lung microvascular endothelial cells (LMECs) and lung tissue homogenate was examined by ELISA. Treg cell differentiation was determined using flow cytometry. The relationships between miR-381, YTHDF1, and IL-18 were investigated using dual-luciferase reporter gene, RIP, and/or RNA pull-down assays. MeRIP assay was employed to determine m⁶A modification of IL-18 mRNA in LMECs. The ubiquitination level of Foxp3 protein in CD4⁺ T cells was analyzed by Co-IP assay.</div></div><div><h3>Results</h3><div>BMSCs-derived exosomes reduced LMECs injury and increased Treg cell differentiation in LIRI, whereas miR-381 inhibition in BMSCs weakened these impacts. Mechanistically, miR-381 inhibited IL-18 translation in LMECs by inhibiting YTHDF1 expression <em>via</em> binding to its 3’-UTR. As expected, YTHDF1 overexpression in LMECs abolished the effects of miR-381-overexpressed exosomes on LMECs injury and Treg cell differentiation. Moreover, LMECs-secreted IL-18 inhibited Treg cell differentiation by promoting the ubiquitination degradation of Foxp3 protein.</div></div><div><h3>Conclusion</h3><div>BMSCs-derived exosomal miR-381 suppressed IL-18 translation in LMECs through binding to YTHDF1 3’-UTR, thus suppressing the ubiquitination degradation of Foxp3 in CD4⁺ T cells, which promoted Treg cell differentiation and mitigated LIRI development.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111440"},"PeriodicalIF":4.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364585","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":"Acyl-CoA long-chain synthetase 1 (ACSL1) protects the endometrium from excess palmitic acid stress during decidualization","authors":"Weijia Gu ,&nbsp;Biya Zeng ,&nbsp;Yi Zhang ,&nbsp;Fanxuan Zhao ,&nbsp;Xiang Lin ,&nbsp;Xinyu Wang ,&nbsp;Na Liu ,&nbsp;Fangying Sun ,&nbsp;Feng Zhou ,&nbsp;Songying Zhang ,&nbsp;Yongdong Dai","doi":"10.1016/j.cellsig.2024.111438","DOIUrl":"10.1016/j.cellsig.2024.111438","url":null,"abstract":"<div><div>Endometrial receptivity relies on the functional and morphological change of endometrium stromal cells (EnSCs) and epithelial cells in the secretory phase. Decidualization of ESCs and transitions in endometrium epithelial cells are crucial for successful uterine implantation and maintaining pregnancy. Accumulated data have demonstrated that decidualization is tightly coordinated by lipid metabolism. However, the lipidomic change and regulatory mechanism in uterine decidualization are still unknown. Our study showed that endometrium stromal cells and decidual stromal cells had different lipidomic profiles. Acyl-CoA long-chain synthetase 1 (ACSL1) which converts fatty acids to acyl-CoA expression was strongly elevated during decidualization. ACSL1 knockdown inhibited stromal-to-decidual cell transition and decreased the decidualization markers prolactin and Insulin-like growth factor-binding protein-1 (IGFBP1) expression through the AKT pathway. Lipid uptake was upregulated in stromal cells while lipid droplet accumulation was downregulated during decidualization. Meanwhile, silencing of <em>ACSL1</em> led to impaired spare respiratory capacity, and downregulation of <em>TFAM</em> expression, indicating robust lipid metabolism. While palmitic acid addition impeded decidualization, overexpression of <em>ACSL1</em> could partially reverse its effect. ACSL inhibitor Triacsin C significantly impeded decidualization in a three-dimensional coculture model consisting of endometrial stromal cells and epithelial cells. Knockdown of <em>ACSL1</em> in stromal cells decreased the expression of the decidualization markers <em>PAEP</em> and <em>SPP1</em> in epithelial cells. Collectively, ACSL1 is essential for uterine decidualization and protects stromal cells from excess palmitic acid stress.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111438"},"PeriodicalIF":4.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342640","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":"Bmal1 upregulates ATG5 expression to promote autophagy in skin cutaneous melanoma","authors":"Tao Lei ,&nbsp;Xin Cai ,&nbsp;Hao Zhang ,&nbsp;Xunping Wu ,&nbsp;Zhimin Cao ,&nbsp;Wen Li ,&nbsp;Xingming Xie ,&nbsp;Bangyan Zhang","doi":"10.1016/j.cellsig.2024.111439","DOIUrl":"10.1016/j.cellsig.2024.111439","url":null,"abstract":"<div><h3>Background</h3><div>Skin cutaneous melanoma (SKCM) is a highly aggressive and malignant tumor that arises from the malignant transformation of melanocytes. In light of the limitations of existing treatment modalities, there is a pressing need to identify new drug targets for SKCM. Aryl-hydrocarbon receptor nuclear translocator-like (ARNTL), also known as Bmal1, is a gene that has been linked to the onset and progression of cancer. However, its role in SKCM remains understudied.</div></div><div><h3>Methods</h3><div>The expression of Bmal1 mRNA and protein was detected using TCGA, GTEx, CCLE, and ULCAN databases. Moreover, survival analysis was performed to investigate the association between Bmal1 and immune invasion and gene expression in immune infiltrating cells <em>via</em> CIBERSORT, R programming, TIMER, Sangerbox, Kaplan-Meier. The study also explored the role of proteins associated with Bmal1 by using R programming and databases (STRING and GSEA). Both <em>in vitro</em> and <em>in vivo</em> studies were conducted to examine the potential role of Bmal1 in SKCM.</div></div><div><h3>Results</h3><div>Compared to normal tissues, the expression level of <em>Bmal1</em> was significantly reduced in SKCM. Which has been associated with its poor prognosis. Similarly, its expression in SKCM was substantially correlated with immune infiltration, while biogenic analysis indicated that it could potentially influence the tumor immune microenvironment (TME) by influencing tumor-associated neutrophils (TANs). Moreover, Bmal1 overexpression suppressed the proliferation and invasion of melanoma cells and enhanced apoptosis, migration, and cell colony formation.</div></div><div><h3>Conclusion</h3><div>This study concluded that Bmal1 is a novel biomarker that functions as both a diagnostic and prognostic indicator for the progression of SKCM.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111439"},"PeriodicalIF":4.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342641","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}