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Published on: October 14, 2016
miR-150 blocks MLL-AF9-associated leukemia through oncogene repression.
Marina Bousquet1, Guoqing Zhuang, Cong Meng
1Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Molecular Cancer Research : MCR
|April 23, 2013
Summary
MicroRNA miR-150 functions as a tumor suppressor in mixed-lineage leukemia (MLL). Restoring miR-150 inhibits leukemia development and targets key oncogenes, offering new therapeutic avenues.
Area of Science:
- Molecular Biology
- Oncology
- Hematology
Background:
- MicroRNA miR-150 is a key regulator of hematopoiesis.
- miR-150 is downregulated in mixed-lineage leukemia (MLL).
Purpose of the Study:
- To investigate the role of miR-150 as a tumor suppressor in MLL.
- To identify miR-150 targets involved in leukemia development.
Main Methods:
- Using MLL-AF9-transformed cells for in vitro and in vivo studies.
- Employing gene expression profiling and shRNA-mediated gene suppression.
- Assessing blast colony formation, cell growth, apoptosis, and leukemia development in transplanted mice.
Main Results:
- Ectopic miR-150 expression inhibited blast colony formation, cell growth, and increased apoptosis in MLL-AF9 cells.
- miR-150 overexpression completely blocked myeloid leukemia development in mice.
- miR-150 regulated over 30 stem cell signature genes and cancer pathway genes.
- Cbl and Egr2 were identified as novel miR-150 targets, and their suppression mimicked miR-150's pro-apoptotic effects.
Conclusions:
- miR-150 acts as a potent tumor suppressor in MLL by targeting multiple oncogenes.
- These findings identify novel therapeutic targets for MLL-AF9-related leukemia.
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