中山大学肿瘤防治中心贝锦新团队近期取得重要工作成果，他们研究提出，PLD1和NF-κB信号之间的正反馈回路促进鼻咽癌的发生。相关研究成果2024年6月15日在线发表于《遗传学报》杂志上。

据介绍，磷脂酶D（PLD）脂质信号酶超家族已广泛参与各种人类恶性肿瘤，但其在鼻咽癌（NPC）中的作用和潜在机制尚不清楚。

研究人员通过转录组学分析了87个NPC和10个对照样品中6个PLD家族成员的表达。研究结果显示，在NPC肿瘤和细胞系中，PLD1都显著上调，这与NPC患者的无病生存率和总生存率较差有关。功能测定进一步阐明了PLD1的致癌作用，证明了它对关键的致瘤过程的关键促进作用，如体外细胞增殖和迁移，以及体内肿瘤生长。

研究数据揭示了PLD1和NF-κB信号通路之间的正反馈回路，从而导致NPC的进展。具体而言，PLD1通过促进RELA（p65）的磷酸化和核转位来增强NF-κB活性，RELA反过来与PLD1的启动子结合，增强其表达。

此外，RELA过表达显著恢复了PLD1耗竭的NPC细胞中的抑制作用。PLD1抑制剂VU0155069的应用显著抑制了患者来源的异种移植物模型中的NPC肿瘤发生。

总之，这一研究结果确定PLD1/NF-κB信号传导是一个正反馈回路，在NPC中具有良好的治疗和预后潜力。

附：英文原文

Title: A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma

Author: Chun-Ling Luo a, Jin-Xin Bei a b c

Issue&Volume: 2024/06/15

Abstract: 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 PLD1's oncogenic role, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation 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-κB activity by facilitating the phosphorylation and nuclear translocation of RELA (p65), which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression significantly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, significantly 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.

DOI: 10.1016/j.jgg.2024.06.004

Source: https://www.sciencedirect.com/science/article/pii/S1673852724001280