DDX5 promotes hepatocellular carcinoma tumorigenesis via Akt signaling pathway.

The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase and also acts as co-activator that contributes to progression and metastasis of various tumours. However, its expression as well as prognostic roles of DDX5 in hepatocellular carcinoma (HCC) remain elusive. In this study, we investigated clinical significance and biological functions of DDX5 in HCC. Our results suggested that DDX5 showed overexpression at both transcriptional and translational levels in HCC tissues compared with adjacent normal tissues. Moreover, DDX5 expression was demonstrated to be correlated with tumor size (p < 0.001), N stage (p = 0.013), M stage (p = 0.006), tumor differentiation (p < 0.001) and American Joint Committee on Cancer (AJCC) stage (p = 0.001). Simultaneously, high DDX5 expression was found to be significantly correlated to worse outcome including Disease free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.032) according to Kaplan-Meier survival analysis. In vitro studies, it suggested that knockdown of DDX5 suppressed HCC cells migration, invasion and epithelial -to- mesenchymal transition (EMT) process. Depletion of DDX5 could promote HCC cells growth. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that PI3K/Akt signaling pathway obtained the highest enrichment. Furthermore, we found that knockdown of DDX5 decreased Akt as well as p-Akt (S473) expressions. Collectively, these findings suggested that DDX5 facilitated HCC cells growth via Akt signaling pathway. DDX5 played a crucial role in HCC proliferation and tumorigenesis and may be a novel prognostic marker and potential therapeutic target for HCC.