DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells

<b>Background:</b> 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. <b>Methods:</b><i>DDX21</i> expression 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. <b>Results:</b> 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. <b>Conclusions:</b> Our results support the oncogenic role of DDX21 in PDAC and uncover a new role for this helicase in the regulation of basal autophagy.