MDPI: Synergism of Proneurogenic miRNAs Provides a More Effective Strategy to Target Glioma Stem Cells (Penalva & Pertsemlidis Labs)

miRNAs function as critical regulators of gene expression and have been defined as contributors to cancer phenotypes by acting as oncogenes or tumor suppressors. Based on these findings, miRNA-based therapies have been explored in the treatment of many different malignancies. The use of single miRNAs has faced some challenges and showed limited success. miRNAs cooperate to regulate distinct biological processes and pathways and, therefore, a combination of related miRNAs could amplify the repression of oncogenic factors and the effect on cancer-relevant pathways. We established that the combination of tumor suppressor miRNAs miR-124, miR-128, and miR-137 is much more effective than single miRNAs in disrupting proliferation and survival of glioma stem cells and neuroblastoma lines and promoting differentiation and response to radiation. Subsequent genomic analyses showed that other combinations of tumor suppressor miRNAs could be equally effective, and its use could provide new routes to target special cancer-initiating cell populations.