TargetScreen: an unbiased approach to identify functionally important microRNA targets.

We recently identified miR-19 as the critical activity for leukemogenesis within the oncogenic 17~92 cluster of microRNAs. ( 1) This finding prompted us to test an unbiased method for pinpointing those miR-19 targets may be key to its oncogenic action. Specifically, we used a large-scale short hairpin RNA screen to identify those miR-19 target genes, whose knockdown could reproduce miR-19's effects on lymphocyte transformation. In this way, we found that miR-19 produces a coordinate clampdown on multiple negative regulators of PI3K-related survival signals. These findings have implications for the therapy of miR-19 expressing tumors. They also validate a new strategy for the unbiased identification of functionally important microRNA target genes. Using the example of miR-19 in leukemia, we will discuss some possibilities and limitations of this new approach.