Identification of targets of tumor suppressor microRNA-34a using a reporter library system

Significance Identification of miRNA targets is necessary for understanding their functions; however, current approaches to screening for specific targets are inadequate. For example, most miRNA target-prediction tools only match the 3′-UTR sequence with the miRNA sequence. We created a screening system for miRNA targets using a reporter library of 4,891 full-length cDNAs inserted into the 3′ UTR of a luciferase gene. Using this system, we identified targets of tumor suppressor miR-34a. Among the identified targets, GFRA3 , which is crucial for growth of breast cancer cells and affects the survival of patients with breast cancer, was directly regulated by miR-34a via the coding region. Our study shows the advantage of this full-length reporter library system in identifying functional targets of miRNAs.