JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

N-Glycosylation Modification of Fzd4 Is Essential for the Fzd4-Wnt-β-Catenin Signalling Axis

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-14 DOI: 10.1111/jcmm.70539

Tianyi Ji, Xiangying Li, Jiachen Li, Guan Wang

{"title":"N-Glycosylation Modification of Fzd4 Is Essential for the Fzd4-Wnt-β-Catenin Signalling Axis","authors":"Tianyi Ji, Xiangying Li, Jiachen Li, Guan Wang","doi":"10.1111/jcmm.70539","DOIUrl":"https://doi.org/10.1111/jcmm.70539","url":null,"abstract":"Wnt signalling is a highly conserved signalling pathway that plays an important role in a variety of biological processes. Frizzled (Fzd) family proteins are receptors for Wnt ligands. The physiological processes involved in mature trafficking of Fzd proteins remain elusive. Here, we identified asparagine residues 59 and 144 as the N-glycosylation modification sites of Fzd4. Sequence analysis of Fzd4 in different species showed that the two asparagine residues were highly conserved. N-glycosylation modification of Fzd4 is indispensable for its maturation and transport to the plasma membrane. N-glycosylation modification enhances the stability of Fzd4 and is also necessary for Fzd4 activity, which promotes Fzd4 interaction with Wnt ligands and co-receptor Norrin. Knockout of Fzd4 in the non-small cell lung cancer (NSCLC) cell line A549 followed by replenishment of Fzd4 glycosylation site mutants inhibited the growth and migration ability of A549 cells in vitro and in vivo. In summary, we identified N-glycosylation modification sites of Fzd4. N-glycosylation modification of Fzd4 is necessary for its stability and activity. When N-glycosylation modification is absent, Fzd4 cannot mediate the Wnt/β-catenin signalling pathway, which can inhibit the proliferation and migration of NSCLC and provide new targets and strategies for the treatment of NSCLC.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-17A Induces Circadian Disruptions Through the Epigenetic Repression of BMAL1 in Mice With Alzheimer's Disease

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70546

Ting Liu, Tian Mao, Jinxuan Fan, Yanjun Shen, Lingxia Xue, Kaili Du, Yang Li, Li Wang, Xiaohui Wang

{"title":"IL-17A Induces Circadian Disruptions Through the Epigenetic Repression of BMAL1 in Mice With Alzheimer's Disease","authors":"Ting Liu, Tian Mao, Jinxuan Fan, Yanjun Shen, Lingxia Xue, Kaili Du, Yang Li, Li Wang, Xiaohui Wang","doi":"10.1111/jcmm.70546","DOIUrl":"https://doi.org/10.1111/jcmm.70546","url":null,"abstract":"Circadian disruptions and neuroinflammation impact nearly all people with Alzheimer's disease (AD), but their relationships with each other and the impact of their interaction on AD remain to be addressed. Here, we found that amyloid (A)-β treatment downregulated brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL) 1 through the hypermethylation of its promoter region in HT22 cells and that the inhibition of DNA methylation ameliorated circadian rhythm disorders and restored BMAL1 protein expression by reversing its hypermethylation in APPswe/PSEN1dE9 (APP/PS1) mice. Critically, increased levels of interleukin (IL)-17A contributed to BMAL1 downregulation through the hypermethylation of its promoter region, thus leading to circadian disruptions in APP/PS1 mice. Moreover, we revealed that the mitogen-activated protein kinase (MAPK) pathway was responsible for IL-17A-induced DNA methyltransferase (DNMT) 1 upregulation. Taken together, we elucidate a new mechanism connecting IL-17A with altered DNA methylation of Bmal1, which results in circadian disturbances in an AD mouse model.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP13 Facilitates the Proliferation of Hepatocellular Carcinoma Cells by Reducing K48/63-Linked Polyubiquitination and Degradation of PRPF6

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70551

Yanyu Jiang, Qing Luo, Xuanchao Zhang, Weichao Yang, Renhao Wang, Qinghe Hu, Zhiyi Liu, Bin Zhang

{"title":"USP13 Facilitates the Proliferation of Hepatocellular Carcinoma Cells by Reducing K48/63-Linked Polyubiquitination and Degradation of PRPF6","authors":"Yanyu Jiang, Qing Luo, Xuanchao Zhang, Weichao Yang, Renhao Wang, Qinghe Hu, Zhiyi Liu, Bin Zhang","doi":"10.1111/jcmm.70551","DOIUrl":"https://doi.org/10.1111/jcmm.70551","url":null,"abstract":"Ubiquitin-specific peptidase 13 (USP13) is a well-characterised deubiquitinating enzyme that plays a critical role in the pathogenesis and progression of various human malignancies. However, the precise mechanisms by which USP13 influences hepatocellular carcinoma (HCC) cell proliferation remain to be fully elucidated. In this study, we confirmed that USP13 expression was upregulated in HCC and correlated with poor prognosis. Further investigation revealed that the knockout of USP13 inhibited HCC cell proliferation, whereas overexpression of USP13 had the opposite effect. Mechanistically, pre-mRNA processing factor 6 (PRPF6) was identified as a potential substrate of USP13 through mass spectrometry analysis. USP13 stabilised the PRPF6 protein by reducing its K48/63-linked polyubiquitination levels and degradation. Ultimately, we demonstrated that the USP13-PRPF6 axis promoted HCC cell proliferation was closely associated with the activation of the AKT-mTOR signalling pathway.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The FLNA Gene in Tumour-Educated Platelets Can Be Utilised to Identify High-Risk Populations for NSCLCs

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70544

Ruiling Zu, Hanxiao Ren, Xing Yin, Xingmei Zhang, Lubei Rao, Pingyao Xu, Dongsheng Wang, Yuping Li, Huaichao Luo

{"title":"The FLNA Gene in Tumour-Educated Platelets Can Be Utilised to Identify High-Risk Populations for NSCLCs","authors":"Ruiling Zu, Hanxiao Ren, Xing Yin, Xingmei Zhang, Lubei Rao, Pingyao Xu, Dongsheng Wang, Yuping Li, Huaichao Luo","doi":"10.1111/jcmm.70544","DOIUrl":"https://doi.org/10.1111/jcmm.70544","url":null,"abstract":"Selective screening of the population based on NSCLC risk is an effective technique for minimising overdiagnosis and overtreatment. Platelets and the components can be used as liquid-biopsy markers, potentially assessing the risk of NSCLC, which are easily deployed in clinical applications. Platelet RNA sequencing datasets were analysed to identify specific genes derived from NSCLC patients and healthy donors. Then, expressions of the selected gene were validated in a clinical trial. Not only the availability of the specific gene in differentiating NSCLC patients from healthy donors but also from patients with benign nodules was estimated respectively. Finally, the values of the specific TEP-gene in metastasis and survival prognosis were also evaluated. FLNA was selected based on the GSE datasets, of which mRNA expression levels were higher in platelets from NSCLC patients than in healthy donors and also higher than in benign patients. To discriminate the malignant patients from the healthy individuals, FLNA got an AUC for the ROC curve of 0.716. When discriminating from the benign individuals, FLNA got an AUC of 0.705. In addition, an AUC of 0.595 was found when the metastatic group was distinguished from the non-metastatic group using the relative quantitative results of FLNA, and it seemed that the high-FLNA-expression group had a poorer long-term survival rate than the low-expression group. These findings suggested that high expression of FLNA in TEPs may indicate the incidence and metastasis of NSCLC and serve as a biomarker for high-risk estimation for NSCLC.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive Analysis of GPSM2: From Pan-Cancer Analysis to Experimental Validation

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70527

Chunjiao Yang, Yuzhe Zhang, Lirong Yan, Aoran Liu, Fang Li, Yanke Li, Ye Zhang

{"title":"Comprehensive Analysis of GPSM2: From Pan-Cancer Analysis to Experimental Validation","authors":"Chunjiao Yang, Yuzhe Zhang, Lirong Yan, Aoran Liu, Fang Li, Yanke Li, Ye Zhang","doi":"10.1111/jcmm.70527","DOIUrl":"https://doi.org/10.1111/jcmm.70527","url":null,"abstract":"G-protein signalling modulator 2 (GPSM2) plays an important role in maintaining cell polarisation and regulating the cell cycle; however, a systematic and comprehensive analysis of GPSM2 in cancer is still lacking. Using extensive multi-omics data, we explored the pan-cancer expression levels of GPSM2 from multiple perspectives and its association with prognosis, diagnosis, tumour stemness, immune-related genes, immune cell infiltration, genomic instability, and response to immunotherapy. We also elucidated the potential pan-cancer biological functions of GPSM2 using gene set enrichment analysis (GSEA) and searched for targeted drugs that affect GPSM2 expression using connectivity map analysis. To elucidate the effect of GPSM2 on colon cancer, we evaluated its effect on the biological behaviour of two colon cancer cell lines. In this study, GPSM2 was systematically analysed and shown to have satisfactory performance in disease diagnosis and prognostic prediction of various cancers. G-protein signalling modulator 2 plays an important role in the genesis and development of various tumours and is a potential tumour diagnostic and prognostic biomarker as well as an anti-cancer therapeutic target.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association Between Circulating Cytokines and Endometriosis: A Mendelian Randomization Study 循环细胞因子与子宫内膜异位症的关系：孟德尔随机研究

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70532

Xiao Xu, Jie Mei, Bin Zhang, Xi-Ya Jiang, Li Wang, Ai-Xi Zhang, Jie-Jie Li, Shun-Xia Chen, Yu-Feng He, Ya-Xing Fang, Lan Zheng, Qin-Qin Jin, Jing-Jing Hu, Shu-Guang Zhou

{"title":"Association Between Circulating Cytokines and Endometriosis: A Mendelian Randomization Study","authors":"Xiao Xu, Jie Mei, Bin Zhang, Xi-Ya Jiang, Li Wang, Ai-Xi Zhang, Jie-Jie Li, Shun-Xia Chen, Yu-Feng He, Ya-Xing Fang, Lan Zheng, Qin-Qin Jin, Jing-Jing Hu, Shu-Guang Zhou","doi":"10.1111/jcmm.70532","DOIUrl":"https://doi.org/10.1111/jcmm.70532","url":null,"abstract":"Existing evidence shows the importance of circulating cytokines in studying female reproductive system dysfunction. Endometriosis (EM) is thought to be associated with multiple immune cytokines, but its causality has not been proven. Utilising Genome-Wide Association Study (GWAS) data, we performed Mendelian randomisation (MR) to assess causality between 41 cytokines and EM. Positive Single Nucleotide Polymorphisms (SNPs) were annotated via Multi-marker Analysis of GenoMic Annotation (MAGMA) and intersected with EM-associated genes from Weighted Gene Co-expression Network Analysis (WGCNA). Shared genes underwent single-gene Gene Set Enrichment Analysis (GSEA). The association of shared genes with endometriosis was validated by the quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method. Two-sample MR identified TNF-Related Apoptosis-Inducing Ligand (TRAIL) as causally linked to EM. Inverse variance weighting (IVW) revealed that elevated TRAIL levels reduced EM risk (β = −0.061, p = 2.267e-6). WGCNA identified DSG 2 (a TRAIL-related gene related to EM). Quantitative analysis based on clinical samples confirmed the low expression of DSG 2 in patients with endometriosis. GSEA indicated DSG 2 participation in many signalling pathways. MR analysis revealed that elevated TRAIL levels significantly reduce the risk of EM. MAGMA and WGCNA analyses identified DSG 2 as a key gene associated with TRAIL. Gene expression analysis combined with GSEA suggested that decreased DSG 2 expression may influence the development of EM through various pathways. These results offer new potential diagnostic markers and therapeutic targets for EM.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IRX5 Promoted SREBP1-Mediated de Novo Fatty Acid Synthesis via HMGN4 in Hepatocellular Carcinoma

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-10 DOI: 10.1111/jcmm.70441

Liying Zhu, Yongjie Xu, Changyudong Huang, Chengcheng Li, Yiqiong Zhang, Xing Li, Wei Pan, Zhu Zeng

{"title":"IRX5 Promoted SREBP1-Mediated de Novo Fatty Acid Synthesis via HMGN4 in Hepatocellular Carcinoma","authors":"Liying Zhu, Yongjie Xu, Changyudong Huang, Chengcheng Li, Yiqiong Zhang, Xing Li, Wei Pan, Zhu Zeng","doi":"10.1111/jcmm.70441","DOIUrl":"https://doi.org/10.1111/jcmm.70441","url":null,"abstract":"Hepatocellular carcinoma (HCC), a prevalent malignant tumour, ranks highly in both morbidity and mortality, and its prevention and treatment need further studies. The transcription factor iroquois homeobox 5 (IRX5) plays an essential role in HCC, whereas little is known about its exact functions and underlying mechanisms in tumour metabolism reprogramming. Besides, as a transcription factor that mainly locates in nuclei, IRX5 lacks a nuclear localisation sequence, which makes uncovering the mechanism of IRX5 translocating into the nuclei of great significance. Here, we first found that both IRX5 and HCC development are highly expressed; IRX5 accelerates de novo fatty acid synthesis and promotes cancer cell proliferation and progression. Moreover, the GST pull-down combined with GC/MS experiments identified an interaction between IRX5 and high-mobility group nucleosomal binding domain 4 (HMGN4). Immunofluorescence analysis showed that IRX5 and HMGN4 colocalised within the nucleus. Coimmunoprecipitation further confirmed their direct interaction. The elevated expression of HMGN4 enhanced the nuclear transport of IRX5. Taken together, our observations suggest that HMGN4 driving IRX5 nuclear translocation promotes HCC development via de novo fatty acid synthesis reprogramming.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ambrisentan Retains Its Pro-Autophagic Activity on Human Pulmonary Artery Endothelial Cells Exposed to Hypoxia in an In Vitro Model Mimicking Diabetes

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-09 DOI: 10.1111/jcmm.70528

Manuela Cabiati, Filippo Biondi, Sandra Ghelardoni, Valentina Casieri, Vincenzo Lionetti, Agnese Sgalippa, Silvia Del Ry, Rosalinda Madonna

{"title":"Ambrisentan Retains Its Pro-Autophagic Activity on Human Pulmonary Artery Endothelial Cells Exposed to Hypoxia in an In Vitro Model Mimicking Diabetes","authors":"Manuela Cabiati, Filippo Biondi, Sandra Ghelardoni, Valentina Casieri, Vincenzo Lionetti, Agnese Sgalippa, Silvia Del Ry, Rosalinda Madonna","doi":"10.1111/jcmm.70528","DOIUrl":"https://doi.org/10.1111/jcmm.70528","url":null,"abstract":"Cardiovascular comorbidities are associated with reduced treatment response in group 1 pulmonary arterial hypertension (PAH). This may result from misdiagnosis of group 2 PH, but it can also be explained as the loss of ability of pulmonary endothelial cells to respond to specific antiremodeling drugs. We evaluated the effects of high glucose (HG) and hyperosmolar stress (high mannitol, HM) on the response of human pulmonary artery endothelial cells (hPAECs) to ambrisentan (AMB), focusing on autophagy, viability, apoptosis and several microRNAs involved in pulmonary arterial remodelling. hPAECs were incubated with 30.5 mM HG or 25 mM HM, with/without 0.02 nM AMB in normoxia (Nx) or hypoxia (Hx) for 24 h. Hx reduced cell survival (p = 0.03) and autophagy (p = 0.02), an effect mimicked by HG and HM only in Nx. In Nx and Hx, AMB reverted the effect of HG, but not HM on autophagy, almost completely or partially, respectively. Compared to Nx, Hx increased the antiapoptotic miR124-3p in vehicle-treated hPAEC (p = 0.002), and induced an opposite effect on antiapoptotic and proliferative miR191-3p. In Nx, AMB induced miR124-3p in HG- (p = 0.04 vs. HG+A_Nx) and HM-treated (p < 0.0001 vs. HM+AMB_Nx) hPAECs, and miR191-3p in HM-treated hPAECs (p = 0.03). In H, A induced a similar effect on miR124-3p in hPAEC exposed to AMB+HM (p = 0.02). In hPAEC exposed to Hx, AMB retains its pro-autophagic effects in an in vitro model mimicking diabetes. miR124-3p and, to a lesser extent, miR191-3p may act as biomarkers of disease and treatment response to specific drugs in patients with PAH and diabetes.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ATP13A2 as a prognostic biomarker and its correlation with immune infiltration in cervical cancer: A retrospective study 作为预后生物标志物的 ATP13A2 及其与宫颈癌免疫浸润的相关性：一项回顾性研究

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-08 DOI: 10.1111/jcmm.70097

Zhi Zhao, Yijie Peng, Yuanyuan Yang, Shuaiyu Li, Jiang Ling, Zhenyu Zhu, Chenfeng He

{"title":"ATP13A2 as a prognostic biomarker and its correlation with immune infiltration in cervical cancer: A retrospective study","authors":"Zhi Zhao, Yijie Peng, Yuanyuan Yang, Shuaiyu Li, Jiang Ling, Zhenyu Zhu, Chenfeng He","doi":"10.1111/jcmm.70097","DOIUrl":"https://doi.org/10.1111/jcmm.70097","url":null,"abstract":"While the oncogene ATP13A2 is reportedly involved in colorectal cancer, its role in cervical cancer (CC) has yet to be fully characterized. In this study, we investigated ATP13A2 as a potential prognostic biomarker of CC. To this end, we compared CC tissues with normal tissues to identify differentially expressed genes, identifying ATP13A2 as a potential marker of CC. Elevated ATP13A2 expression levels were identified in CC samples compared to noncancerous samples across various data sets, with further immunohistochemical validation. Functional enrichment analysis revealed that ATP13A2 plays an essential role in the CXCL12-activated CXCR4 signalling pathway and chemotaxis regulation, which may alter immune infiltration. Notably, increased ATP13A2 levels were associated with poor overall survival. Furthermore, multiple clinical characteristics were significantly associated with ATP13A2 expression. Additionally, tumour bacterial infiltration was assessed using weighted co-expression network analysis, revealing a relationship between ATP13A2 expression and bacteria in the CC tumour microenvironment. Our results suggest that ATP13A2 is a promising diagnostic and prognostic marker for CC. However, further large-scale studies are needed to fully elucidate the mechanisms underlying the involvement of ATP13A2 in CC.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tspo Depletion Exacerbates Steatosis Through Fatty Acid Uptake

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-04-07 DOI: 10.1111/jcmm.70500

Yuchang Li, Liting Chen, Chantal Sottas, Nrupa Dinesh Patel, Mahima Chandrakant Raul, Vassilios Papadopoulos

{"title":"Tspo Depletion Exacerbates Steatosis Through Fatty Acid Uptake","authors":"Yuchang Li, Liting Chen, Chantal Sottas, Nrupa Dinesh Patel, Mahima Chandrakant Raul, Vassilios Papadopoulos","doi":"10.1111/jcmm.70500","DOIUrl":"https://doi.org/10.1111/jcmm.70500","url":null,"abstract":"Previous studies demonstrated that Tspo loss causes simple steatosis (SS) in hepatocytes in vitro. However, its effect on SS in vivo remains unclear. In this study, we hypothesise that Tspo loss promotes early-stage MASLD. WT and Tspo KO rats were fed a Gubra Amylin NASH (GAN) diet for 8 weeks to induce SS. Tspo KO rats fed the GAN diet (KO GAN) exhibited increased insulin resistance, higher plasma cholesterol, and elevated hepatic triacylglycerol (TAG) levels, along with higher de novo lipogenesis (DNL) and free fatty acid (FFA) uptake, evidenced by increased fatty acid synthase (FASN) and CD36 expression. The Acyl-coenzyme A binding protein/diazepam-binding inhibitor-TSPO complex facilitated FA transport to the mitochondria, where carnitine palmitoyltransferase 1A (CPT1A) directed them for β-oxidation. TSPO interacted with CPT1A in the outer mitochondrial membrane, while its depletion increased CPT1A expression, boosting FA oxidation. Primary Tspo KO rat hepatocytes and stably overexpressed CD36 (CD36_OE) in Huh7 cells displayed impaired mitochondrial function and compromised mitochondrial membrane potential. KO GAN livers had significantly elevated AcCoA, which acetylated RAPTOR, activating mTORC1 to suppress autophagy. Overall, Tspo deficiency exacerbates the advancement of SS by enhancing CD36-mediated FFA uptake, elevating AcCoA levels, compromising mitochondrial function and impairing autophagy during the early stages of MASLD.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0