DDX24 promotes metastasis by regulating RPL5 in non‐small cell lung cancer

Abstract

Abstract Purpose Non‐small cell lung cancer (NSCLC) is a leading cause of cancer death, and metastasis is a crucial determinant of increased cancer mortality. DDX24 has garnered increased attention due to its correlation with tumorigenesis and malignant progression. However, the correlation between DDX24 and NSCLC remains unclear. Methods DDX24 expression in NSCLC tissues and survival rate of patients was analyzed using bioinformatic analysis. Transwell assays, wound‐healing assays, and tail vein lung colonization models were employed to determine the role of DDX24 in migration and invasion in vitro and in vivo. We searched for DDX24‐interacting proteins using co‐immunoprecipitation followed by mass spectroscopy and verified the interaction. The influence of DDX24 on RPL5 expression and ubiquitination was examined using protein stability assays. Results DDX24 expression was upregulated in NSCLC cell lines and tumors of patients, particularly those with high tumor grades. A high DDX24 level was also correlated with a poor prognosis. DDX24 upregulation enhanced the migration and invasion ability of NSCLC cells, whereas its downregulation had the opposite effects. In vivo xenograft experiments confirmed that tumors with high DDX24 expression had higher metastatic abilities. The interaction between DDX24 and RPL5 promoted its ubiquitination and destabilized it. Conclusions DDX24 acted as a pro‐tumorigenic factor and promoted metastasis in NSCLC. DDX24 interacted with RPL5 to promote its ubiquitination and degradation. As a result, targeting DDX24/RPL5 axis may provide a novel potential therapeutic strategy for NSCLC.

Keywords

• DDX24
• metastasis
• non‐small cell lung cancer
• RPL5
• ubiquitination