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.
Mavrakis
Konstantinos J
KJ
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Wendel
Hans-Guido
HG
D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000628:therapy; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference
C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases