Figure 1.

Modification of tumor suppressor miRNA with 5-FU as a novel miRNA-based therapeutic strategy. The guide strand of tumor suppressor miR-15a can be modified by replacing the uracils with a chemotherapeutic nucleoside analog, 5-FU (green), to make 5-FU-miR-15a. The passenger strand remains intact to minimize off-target effects. The 5-FU-miR-15a has several unique properties derived by integrating the therapeutic powers of miR-15a with 5-FU to impact multiple targets/pathways, such as stemness, apoptosis and cell cycle in CRC and PDAC (down arrows represent downregulated expression and up arrow represents increased effect). In addition, 5-FU-miR-15a can be delivered without the use of a delivery vehicle. This novel modification strategy can potentially be applied to other tumor suppressor miRNA candidates and cancer types.