Screening microRNA-196 targets in 11q23-translocation acute myeloid leukemia reveal mechanisms maintaining leukemia stemness with therapeutic potential
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PROVIDER: PRJNA305517 | ENA |
REPOSITORIES: ENA
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Project description:microRNA are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify one such microRNA, miR-196b, is essential for MLL-AF9 leukemia initiation and maintenance. To discover how miR-196b contributes to leukemogenesis, we utilized multiple unbiased approaches that identified and functionally screened miR-196b target activity in AML. Our studies resolved how conflicting networks of miRNA-regulated targets are integrated during leukemogenesis. This work uncovered two miR-196b direct targets, the cell cycle regulator Cdkn1b (p27Kip1) and Polycomb group member Phc2, that independently cooperate with MLL-AF9 to promote leukemogenesis by regulating stem cell transcriptional programs. Finally, we found that therapeutic disruption of miR-196b direct targeting of Cdkn1b suppresses leukemogenesis. Overall design: Identify the AML-relevant miR-196b direct targets using a biotinylated miRNA mimic as bait to capture biotinylated miR-containing RISC complexes with assoicated mRNA targets. Associated mRNA targets are then puified using the biotin-streptavidin system and identified by microarray.
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