miRNAs as therapeutic modulators to treat blood cancers
Inventors: Francisco Navarro, Judy Lieberman
Invention Types: Therapeutics
Research Areas: Oncology/Hematology
Keywords: For More Information Contact: Dietz, Ryan
MicroRNAs (miRNAs) are small non-coding RNAs that influence gene expression in order to regulate cell processes including differentiation and survival. Altered activity of miRNAs is implicated in leukemogenesis and the pathogenesis of cancer in general.
miR-34a loss is observed in cases of glioma, neuroblastoma, pancreatic cancer, and chronic myelogenous leukemia. The lab of Judy Lieberman at Boston Children’s has demonstrated that miR-34a is a key regulator of hematopoiesis that acts as a tumor suppressor to help prevent blood cancers. By studying K562 cells, a progenitor blood cell line with the potential to differentiate into either megakaryocytes or red blood cells, the researchers found that miR-34a facilitates differentiation to a megakaryocyte state. miR-34a does this by decreasing expression of the transcription factor MYB, a key regulator of multiple decision forks in hematopoiesis. Also, the researchers found that overexpression of miR-34a induces cell cycle arrest and blocks proliferation by repressing CDK4 and CDK6. This supports the role of miR-34a as a tumor suppressor and suggests further exploration into the use of RNAi-based drugs to mimic tumor suppressor miRNAs or antagonize the function of oncogenic miRNAs in blood cancers.
• Therapeutic activators of miR-34a expression or function as a treatment for cancers with low miR34-a levels, including chronic myelogenous leukemia, glioma, neuroblastoma and pancreatic cancer
• Mimics of miR34-a as a treatment for the above cancers
• miRNA34-a is a tumor suppressor known to have decreased expression in specific cancer types
• Targets of miR-34a are known and include MYB, CDK4 and CDK6
Collaboration or license opportunities available
Key Publications: Navarro F, Gutman D, Meire E, Cáceres M, Rigoutsos I, Bentwich Z, Lieberman J. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood. 2009 Sep 3;114(10):2181-92. doi: 10.1182/blood-2009-02-205062. Epub 2009 Jul 7. PubMed PMID: 19584398.
US Patent #8,389,486