DEAD-box RNA helicase 46 (DDX46) has recently been identified as a candidate oncogene in several types of human malignancies. To date, the role of DDX46 in gastric cancer has not been determined. The purpose of the current study was to explore the role of DDX46 in gastric cancer and the potential mechanism. DDX46-silecing or overexpressing gastric cancer cell lines were established to validate the role of DDX46. Our results showed that the expression of DDX46 was significantly increased in gastric cancer tissues and cell lines. Knockdown of DDX46 suppressed the proliferation and invasion of gastric cancer cells. Whereas, DDX46 overexpression enhanced the cell proliferation and invasion of gastric cancer cells. Furthermore, knockdown of DDX46 markedly suppressed the tumor growth of xenografts. Research into the mechanism revealed that DDX46 depletion inhibited the Akt/GSK-3β/β-catenin signaling pathway in gastric cancer cells. Notably, activation of Akt or β-catenin overexpression reversed the DDX46 depletion-mediated anti-cancer effect. In conclusion, these findings indicated that DDX46 exerted an oncogenic role in gastric cancer via regulating the Akt/GSK-3β/β-catenin signaling pathway. Thus, DDX46 might be utilized as a therapeutic anti-cancer target.

DEAD-box RNA解旋酶46（DDX46）最近已被鉴定为几种人类恶性肿瘤的候选癌基因。迄今为止，尚未确定DDX46在胃癌中的作用。本研究的目的是探讨DDX46在胃癌中的作用及其潜在机制。建立了可降解DDX46或过表达的胃癌细胞系，以验证DDX46的作用。我们的结果表明，DDX46在胃癌组织和细胞系中的表达明显增加。抑制DDX46抑制胃癌细胞的增殖和侵袭。而DDX46的过表达增强了胃癌细胞的增殖和侵袭能力。此外，击倒DDX46明显抑制异种移植物的肿瘤生长。机制研究表明，DDX46的消耗抑制了胃癌细胞中的Akt /GSK-3β/β-catenin信号通路。值得注意的是，Akt或β-连环蛋白过表达的激活逆转了DDX46耗竭介导的抗癌作用。总之，这些发现表明，DDX46通过调节Akt /GSK-3β/β-catenin信号传导途径在胃癌中发挥致癌作用。因此，DDX46可以用作治疗性抗癌靶标。