Abstract: Background and purpose: DDX46 plays critical roles in cellular metabolism, and in many cases it has been implicated in cellular proliferation. The expression pattern of DDX46 in tumor tissues and its biologic role in neoplastic transformation have rarely been reported previously. This study aimed to elucidate the role of DDX46 in regulating the malignant process of esophageal squamous cell carcinoma. Methods: Lentivirus-mediated RNA interference was applied to silencing DDX46 in esophageal squamous carcinoma cell line TE-11. Cell growth was monitored using high-content screening (HCS). Cell colony-forming capacity was measured by colony formation assay. Cell apoptosis was determined by flow cytometry. Furthermore, the changes of proteins related to PI3K-Akt-mTOR and autophagy were measured by Western blot. Results: Lentivirus-mediated RNAi efficiently decreased DDX46 expression in TE-11 cells (P<0.001). DDX46 silencing led to decreased cell growth (P<0.01), reduced the number and size of cell colonies (P<0.01), and increased the percentage of apoptotic cells in TE-11 (P<0.01). Moreover, DDX46 silencing induced the apparent down-regulation of PIK3CG, Akt, P-Akt and mTOR (P<0.01), and significantly increased expression of Beclin 1 and LC3 (P<0.01), without change in expression level of PTEN (P>0.05). Conclusion: DDX46 plays an essential role in the progression of esophageal squamous cell carcinoma, and DDX46-mediated regulation of autophagy and apoptosis probably affects tumorigenesis in esophageal squamous cell carcinoma via PI3K-Akt-mTOR signaling pathway.

Key words: DDX46, Esophageal squamous cell carcinoma, Growth, Apoptosis, Autophagy