Clinical Laboratory Medicine Center, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan, P.R. China.
Cancer Research Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, P.R. China.
Aging (Albany NY). 2024 Apr 25;16(8):7174-7187. doi: 10.18632/aging.205750.
Glioma is the most frequently diagnosed primary brain tumor and typically has a poor prognosis because of malignant proliferation and invasion. It is urgent to elucidate the mechanisms driving glioma tumorigenesis and develop novel treatments to address this deadly disease. Here, we first revealed that PDZK1 is expressed at high levels in gliomas. Promoter hypomethylation may cause high expression of PDZK1 in glioma. Knockdown of PDZK1 inhibits glioma cell proliferation and invasion . Mechanistically, further investigations revealed that the loss of PDZK1 expression by siRNA inhibited the activation of the AKT/mTOR signaling pathway, leading to cell cycle arrest and apoptosis. Clinically, high expression of PDZK1 predicts a poorer prognosis for glioma patients than low expression of PDZK1. Overall, our study revealed that PDZK1 acts as a novel oncogene in glioma by binding to AKT1 and maintaining the activation of the AKT/mTOR signaling pathway. Thus, PDZK1 may be a potential therapeutic target for glioma.
神经胶质瘤是最常见的原发性脑肿瘤，由于恶性增殖和侵袭，通常预后不良。阐明驱动神经胶质瘤发生的机制并开发新的治疗方法来治疗这种致命疾病迫在眉睫。在这里，我们首次揭示 PDZK1 在神经胶质瘤中表达水平较高。启动子低甲基化可能导致 PDZK1 在神经胶质瘤中高表达。敲低 PDZK1 可抑制神经胶质瘤细胞的增殖和侵袭。机制研究进一步表明，siRNA 下调 PDZK1 表达可抑制 AKT/mTOR 信号通路的激活，导致细胞周期停滞和细胞凋亡。临床上，PDZK1 高表达预示着神经胶质瘤患者的预后比 PDZK1 低表达差。总之，我们的研究表明，PDZK1 通过与 AKT1 结合并维持 AKT/mTOR 信号通路的激活，在神经胶质瘤中充当一种新型致癌基因。因此，PDZK1 可能是神经胶质瘤的一个潜在治疗靶点。
