Other
23 Authors
- Jiang X,
- Liu PP,
- Arnovitz S,
- Price C,
- Elkahloun AG,
- Rowley JD,
- Le Beau MM,
- Li Z,
- Xu M,
- Gurbuxani S,
- Li Y,
- Chen P,
- Mulloy JC,
- Wiley A,
- Cao D,
- Chen J,
- Hong GM,
- Neilly MB,
- Huang H,
- Kunjamma RB,
- He C,
- Wunderlich M,
- Larson RA
| First Author | Chen P | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 28 | Pages | 11511-6 |
| PubMed ID | 23798388 | Mgi Jnum | J:198699 |
| Mgi Id | MGI:5499022 | Doi | 10.1073/pnas.1310144110 |
| Citation | Chen P, et al. (2013) miR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia-rearranged leukemia. Proc Natl Acad Sci U S A 110(28):11511-6 |
| abstractText | MicroRNAs (miRNAs), small noncoding RNAs that regulate target gene mRNAs, are known to contribute to pathogenesis of cancers. Acute myeloid leukemia (AML) is a group of heterogeneous hematopoietic malignancies with various chromosomal and/or molecular abnormalities. AML with chromosomal translocations involving the mixed lineage leukemia (MLL) gene are usually associated with poor survival. In the present study, through a large-scale, genomewide miRNA expression assay, we show that microRNA-9 (miR-9) is the most specifically up-regulated miRNA in MLL-rearranged AML compared with both normal control and non-MLL-rearranged AML. We demonstrate that miR-9 is a direct target of MLL fusion proteins and can be significantly up-regulated in expression by the latter in human and mouse hematopoietic stem/progenitor cells. Depletion of endogenous miR-9 expression by an appropriate antagomiR can significantly inhibit cell growth/viability and promote apoptosis in human MLL-rearranged AML cells, and the opposite is true when expression of miR-9 is forced. Blocking endogenous miR-9 function by anti-miRNA sponge can significantly inhibit, whereas forced expression of miR-9 can significantly promote, MLL fusion-induced immortalization/transformation of normal mouse bone marrow progenitor cells in vitro. Furthermore, forced expression of miR-9 can significantly promote MLL fusion-mediated leukemogenesis in vivo. In addition, a group of putative target genes of miR-9 exhibited a significant inverse correlation of expression with miR-9 in a series of leukemia sample sets, suggesting that they are potential targets of miR-9 in MLL-rearranged AML. Collectively, our data demonstrate that miR-9 is a critical oncomiR in MLL-rearranged AML and can serve as a potential therapeutic target to treat this dismal disease. |
