The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2.

Acquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA array analysis was performed to examine the microRNA expression profile. Promoter activity and microRNA targets were assessed with luciferase reporters. Cell migration capacity was assessed by either the transwell or scratch assay. In isolated subpopulations with high migration capacity, the expression levels of the cluster increased in accordance with the increased expression of the short transcript, a host gene of the cluster. E2F1-binding sequences were involved in the basic transcription activity of the short expression, and E2F1-small-interfering (si)RNA treatment reduced the expression of both the and clusters. Overexpression experiments showed that and promoted cell migration, but the opposite effect was observed with . Forkhead box P2 (FOXP2) mRNA and protein levels were reduced by both/either and . Furthermore, FOXP2 siRNA treatment significantly promoted cell migration. Our findings demonstrated a novel role of the cluster in cell migration through targeting FOXP2, with potential implications for the development of microRNA-based therapy targeted at inhibiting cancer migration.