The RNA-binding protein DDX39B promotes colorectal adenocarcinoma progression by stabilizing DCLK1

DDX39B, a member of the DEAD-box (DDX) RNA helicase family, plays a pivotal role in the post-transcriptional regulation of diverse pathological processes, including tumor progression, viral replication, and neurodegenerative disorders. In this study, we investigated the functional significance of DDX39B in the proliferation and metastasis of colon adenocarcinoma (COAD) and sought to uncover its underlying molecular mechanism. Our findings revealed that DDX39B was markedly upregulated in COAD tumor tissues, and its elevated expression correlated with poor patient prognosis. Functional assays, both in vitro and in vivo, demonstrated that DDX39B substantially enhanced the proliferative and metastatic potential of COAD cells. Mechanistically, DDX39B expression was positively associated with Ki67 levels and was found to facilitate epithelial-mesenchymal transition (EMT) in COAD. As an RNA-binding protein (RBP), DDX39B increased the stability of DCLK1-B mRNA, a variant highly expressed in colorectal cancer known to promote cancer stemness, thereby augmenting its protein expression. Notably, silencing of DCLK1-B effectively abrogated the pro-metastatic effects induced by DDX39B overexpression. Collectively, our results offered novel insights into the oncogenic role of DDX39B and highlighted its potential as a therapeutic target in COAD.