期刊
CELL CYCLE
卷 9, 期 11, 页码 2080-2084出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.11.11807
关键词
microRNA; targets; miR-19; T-cell leukemia
类别
资金
- Geoffrey Beene Cancer Center
- Leukemia Research Foundation
- Louis V. Gerstner Foundation
- May and Samuel Rudin Foundation
- William and Blanche Foundation
- NIH [R01-CA142798-01]
We recently identified miR-19 as the critical activity for leukemogenesis within the oncogenic 17 similar to 92 cluster of microRNAs. 1 This finding prompted us to test an unbiased method for pinpointing those miR-19 targets that 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.
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