DDX52 knockdown inhibits the growth of prostate cancer cells by regulating c-Myc signaling

Abstract

Background

DDX52 is a type of DEAD/H box RNA helicase that was identified as a novel prostate cancer (PCa) genetic locus and possible causal gene in a European large-scale transcriptome-wide association study. However, the functions of DDX52 in PCa remain undetermined. The c-Myc oncogene plays a crucial role in the development of PCa, but the factors that regulate the activity of c-Myc in PCa are still unknown.

Methods

We determined DDX52 protein levels in PCa tissues using immunohistochemistry (IHC). DDX52 expression and survival outcomes in other PCa cohorts were examined using bioinformatics analysis. The inhibition of DDX52 via RNA interference with shRNA was used to clarify the effects of DDX52 on PCa cell growth in vitro and in vivo. Gene set enrichment analysis and RNA sequencing were used to explore the signaling regulated by DDX52 in PCa. Western blotting and IHC were used to determine the possible DDX52 signaling mechanism in PCa.

Results

DDX52 expression was upregulated in PCa tissues. Bioinformatics analysis showed that the level of DDX52 further increased in advanced PCa, with a high DDX52 level indicating a poor outcome. In vitro and in vivo experiments showed that downregulating DDX52 impeded the growth of PCa cells. High DDX52 levels contributed to activating c-Myc signaling in PCa patients and PCa cells. Furthermore, DDX52 expression was regulated by c-Myc and positively correlated with c-Myc expression in PCa.

Conclusion

DDX52 was overexpressed in PCa tissues in contrast to normal prostate tissues. DDX52 knockdown repressed the growth of PCa cells in vitro and in vivo. Deleting c-Myc inhibited DDX52 expression, which affected the activation of c-Myc signaling.