2025年9月10日,浙江大学良渚实验室、东部战区总医院国家肾脏疾病临床医学研究中心刘志红教授、俞晓敏研究员、周青教授团队在《自然》(Nature)杂志发表了题为“Loss-of-function mutations in PLD4 lead to systemic lupus erythemato...2025年9月10日,浙江大学良渚实验室、东部战区总医院国家肾脏疾病临床医学研究中心刘志红教授、俞晓敏研究员、周青教授团队在《自然》(Nature)杂志发表了题为“Loss-of-function mutations in PLD4 lead to systemic lupus erythematosus”论文(DOI:10.1038/s41586-025-09513-x),证实人类PLD4缺陷可导致系统性红斑狼疮(SLE)并阐明了其致病机制,为SLE的精准诊疗提供了重要的理论依据。展开更多
Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the...Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.展开更多
文摘2025年9月10日,浙江大学良渚实验室、东部战区总医院国家肾脏疾病临床医学研究中心刘志红教授、俞晓敏研究员、周青教授团队在《自然》(Nature)杂志发表了题为“Loss-of-function mutations in PLD4 lead to systemic lupus erythematosus”论文(DOI:10.1038/s41586-025-09513-x),证实人类PLD4缺陷可导致系统性红斑狼疮(SLE)并阐明了其致病机制,为SLE的精准诊疗提供了重要的理论依据。
基金This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)+2 种基金National Natural Science Foundation(82261160657)Chang Jiang Scholars Program(J.-X.B.)Special Support Program of Guangdong(J.-X.B.)。
文摘Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.
