DDX55 promotes HCC progression via interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

The involvement of DEAD-box helicase 55 (DDX55) in oncogenesis has been suggested, but its biological role in hepatocellular carcinoma (HCC) remains unknown. The present study verified the upregulation of DDX55 in HCC tissues compared with non-tumor controls. And DDX55 displayed the highest prognostic values among DEAD-box protein family for the recurrence-free survival and overall survival of HCC patients. In addition, effects of DDX55 on promoting HCC cell proliferation, migration and invasion were determined ex vivo and in vivo. Mechanistically, we revealed that DDX55 could interact with BRD4 to form a transcriptional regulatory complex that positively regulated PIK3CA transcription. Following that, β-catenin signaling was activated in a PI3K/Akt/GSK-3β dependent manner, thus inducing cell cycle progression and epithelial-mesenchymal transition. Intriguingly, both DDX55 mRNA and protein were identified in the exosomes derived from HCC cells. Exosomal DDX55 was implicated in intercellular communication between HCC cells with high or low DDX55 levels and between HCC cells and endothelial cells, thereby promoting malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.