DEAD-Box Helicase 5(DDX5), also known as P68, is one of the founding members of the DEAD-Box helicase superfamily and it plays a key role in RNA metabolism. Several studies have reported that DDX5 is involved in many types of tumors through abnormal expression, but the detailed mechanism of DDX5 in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we demonstrate that the level of DDX5 is a negative prognostic factor for ESCC. The obtained results indicated that decreased expression of DDX5 inhibits ESCC cell proliferation and metastasis. Further experiments suggested that CDK2, Cyclin D1 and Vimentin were downregulated, while E-cadherin was upregulated after DDX5 was knocked down. In addition, DDX5 was positively correlated with the expression of BIP, phospho-eIF2α, phospho-PERK and P62, suggesting that knockdown of DDX5 can inhibit endoplasmic reticulum(ER) stress and promote the recovery of autophagy flux. Therefore, this study demonstrates that the downregulation of DDX5 in ESSC correlates to lower malignancy and presents a novel target for the development of new treatment strategies.

DEAD-Box解旋酶5（DDX5），也称为P68，是DEAD-Box解旋酶超家族的创始成员之一，它在RNA代谢中起关键作用。几项研究报道，DDX5通过异常表达参与多种类型的肿瘤，但尚不清楚DDX5在食管鳞状细胞癌（ESCC）中的详细机制。在这项研究中，我们证明DDX5的水平是ESCC的阴性预后因素。获得的结果表明，DDX5表达的降低抑制了ESCC细胞的增殖和转移。进一步的实验表明CDK2，Cyclin D1和波形蛋白被下调，而DDX5被敲除后E-钙粘蛋白被上调。此外，DDX5与BIP，磷酸化eIF2α，磷酸化PERK和P62的表达呈正相关，提示敲低DDX5可以抑制内质网应激并促进自噬通量的恢复。因此，这项研究证明了ESSC中DDX5的下调与恶性程度降低相关，并为开发新的治疗策略提出了新的靶标。