DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome‐mediated cell‐cell communication

Abstract

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. DDX55 displayed the highest prognostic values among the DEAD‐box protein family for recurrence‐free survival and overall survival of HCC patients. In addition, the effects of DDX55 in the promotion of 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 the malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.

Concurrent remodelling of nucleolar 60S subunit precursors by the Rea1 ATPase and Spb4 RNA helicase

“…Two recent studies reported that the human Spb4 homolog DDX55 is strongly upregulated in various lung cancers and hepatocellular carcinoma (HCC) tissues promoting HCC cell proliferation and migration ( Cui et al, 2021 ; Yu et al, 2022 ). Thus, the obtained insights into the Spb4 function for ribosome biogenesis could be of relevance for medical studies and treatment of such cancer types.…”

Oxeiptosis core genes and their multi-omics analysis in hepatocellular carcinoma

“…Oxeiptosis is a specific cellular response to ROS generated by oxidative stress with the potential to induce In this study, the enrichment analysis of biological functions and signaling pathways, the results seem to indicate that OCGs are closely related to both cell proliferation and death, including biological processes such as chromosome structure, mitotic processes, and cell cycle. We noticed that OCGs contain members of several gene families participate in many malignancy-related biological processes, including T-complexpolypeptide1 family, [24,25] Dead-box family [26][27][28][29] and heterogeneous nuclear ribonucleoprotein (hnRNPs) family. hnRNPs is a class of RNA-binding proteins that acts synergistically with the dead-box family in eukaryotes.…”

Extracellular vesicles and cancer stemness in hepatocellular carcinoma – is there a link?

“…TMPRSS2-enriched exosomes were found to suppress the packaging of pro-tumoral nidogen into exosomes and inhibit proliferation and migration of immortalized hepatic cell ( 12 ). In addition, various molecules, including DEAD-box helicase 55 (DDX55), CPE, miR-3129, LINC00161, clathrin light chain A (CTLA), and miR-25, were found to be enriched in cancer-derived exosomes and induce cell proliferation ( 10 , 19 , 21 – 24 ). Signaling alterations upon sEV treatment primarily involved EMT markers, Wnt/β-catenin signaling, and cell cycle pathways ( 19 , 21 , 23 ).…”

“…In addition, various molecules, including DEAD-box helicase 55 (DDX55), CPE, miR-3129, LINC00161, clathrin light chain A (CTLA), and miR-25, were found to be enriched in cancer-derived exosomes and induce cell proliferation ( 10 , 19 , 21 – 24 ). Signaling alterations upon sEV treatment primarily involved EMT markers, Wnt/β-catenin signaling, and cell cycle pathways ( 19 , 21 , 23 ). These findings suggest potential mechanisms behind the crosstalk between drug resistance pathways and proliferation signaling via sEVs in HCC.…”