Arresting of miR-186 and releasing of H19 by DDX43 facilitate tumorigenesis and CML progression.

ABSTRACT

Cancer-testis (CT) antigens, rarely in normal tissues except testis, are expressed in many tumor types. In recent years, DDX43 has been shown to be expressed in several malignancies. However, the role of DDX43 during tumorigenesis is not well established. In the present study, we explored the function of DDX43 in chronic myeloid leukemia (CML). We found that DDX43 overexpression in CML cell lines enhanced survival and colony formation, inhibited cell apoptosis, promoted tumorigenesis, and CML progression. In contrast, silencing of DDX43 inhibited cell survival and tumorigenesis. Upregulated H19 and downregulated miR-186 were identified in DDX43-transfected cells. Furthermore, we demonstrated that miR-186 targeted DDX43, and overexpressed miR-186 increased apoptosis and decreased cell survival. We also showed that DDX43 regulated the expression of H19 through demethylation and silencing H19 inhibited cell survival. Taken together, these results indicate that DDX43 provides critical support to the progression of CML by enhancing cell survival, colony formation, and inhibiting cell apoptosis, thereby implicating DDX43 as a potential therapeutic target in CML.