miRNA synergism, combination of pro-neurogenic miRNAs as a more effective strategy to target neural derived tumors

Tumor suppressor miRNAs have been explored as treatment agents in cancer therapy. Most strategies consist of using a single miRNA mimics and present many disadvantages that include the amount of reagent required and the diluted effect on target genes. miRNAs work in a cooperative fashion to regulate distinct biological processes and pathways. This information can be used to design more efficient ways to target cancer cells via miRNA combinations. We have shown that miR-124, -128 and -137 function synergistically to regulate neurogenesis. We proceeded to use a combination of these three miRNAs to treat glioblastoma and neuroblastoma cells. We determined that miR-124, -128 and -137 combined treatment is much more effective than single miRNAs in disrupting cell proliferation and survival and in promoting differentiation and response to radiation. Transcriptomic analysis indicated that transcription regulation, angiogenesis, RNA metabolism and neuronal differentiation are among the main biological processes affected by the transfection of this miRNA combination. Finally, in search of other combinations to be explored in therapy, we identified a miRNA cluster based on target predictions and established miR-29, -101, and -218 as an alternative combination to target neuroblastoma and glioblastoma cells.