文章：

DDX21调控胰腺癌细胞周期进程与自噬

DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells

原文发布日期：7 February 2025

DOI: 10.3390/cancers17040570

类型: Article

开放获取: 是

英文摘要：

Background:Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome of patients, only ~20% of them are eligible due to advanced disease at diagnosis. Thus, the development of new therapeutic approaches is a master priority for an improved management of this cancer. The helicase DDX21 was proposed as a prognostic marker in several tumors, including PDAC.Methods:DDX21expression was evaluated in PDAC samples and cell lines; RNA sequencing and bioinformatics analyses of DDX21-depleted PANC-1 silenced cells; functional analyses of autophagy, cell cycle and proliferation.Results:DDX21 is expressed at higher levels in liver metastasis of PDAC patients. Transcriptomics analyses of DDX21-depleted cells revealed an enrichment in genes involved in autophagy and cell cycle progression. The inactivation of DDX21 by RNA interference enhanced the basal autophagic flux and altered the cell cycle by reducing the rate of G1-S transition. Coherently, PDAC cell proliferation and clonogenic activity was significantly reduced.Conclusions:Our results support the oncogenic role of DDX21 in PDAC and uncover a new role for this helicase in the regulation of basal autophagy.

摘要翻译： 

背景：胰腺导管腺癌（PDAC）是一种高度致命的癌症。其预后不良主要归因于晚期诊断及化疗耐药性的产生。尽管手术切除改善了患者的临床结局，但由于诊断时疾病已进展至晚期，仅有约20%的患者符合手术条件。因此，开发新的治疗策略是改善该癌症管理的重要优先事项。解旋酶DDX21已被提出作为包括PDAC在内的多种肿瘤的预后标志物。 方法：评估PDAC样本及细胞系中DDX21的表达水平；对DDX21敲低的PANC-1沉默细胞进行RNA测序及生物信息学分析；对自噬、细胞周期及增殖功能进行分析。 结果：DDX21在PDAC患者的肝转移灶中表达水平更高。对DDX21敲低细胞的转录组学分析显示，参与自噬和细胞周期进程的基因富集。通过RNA干扰使DDX21失活可增强基础自噬流，并通过降低G1-S期转换速率改变细胞周期。相应地，PDAC细胞的增殖和克隆形成能力显著降低。 结论：我们的研究结果支持DDX21在PDAC中发挥致癌作用，并揭示了该解旋酶在基础自噬调控中的新功能。

原文链接：

DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells