(R344) Developing miR-506-3p Mimics with Enhanced Differentiation-Inducing Activity

Nakya Mesa-Diaz (Texas State University)| Liqin Du (Texas State University)

Neuroblastoma is one of the most prominent childhood cancers that results from the failure of neural crest cell differentiation. Inducing cell differentiation is a vital therapeutic strategy for neuroblastoma. MicroRNAs (miRNAs) are a class of endogenously expressed RNAs that regulate expression of target genes by complementary binding to the 3’ untranslated region (3’UTR) of mRNA. Previous studies have shown the miRNA-506-3p seed family to be a strong inducer of neuroblastoma cell differentiation. Differentiation-inducing miRNA mimics, synthetic RNA molecules that imitate the mature miRNA duplexes and their functions, are potential therapeutic agents for neuroblastoma differentiation therapy. In the effort to develop miR-506-3p-based differentiation agents, we identified mutant miRNA-506-3p mimics that potentially have enhanced differentiation-inducing activity based on the predicted interaction of the mutant miR-506-3p with its key differentiation-regulating targets, STAT3 and CDK4, suggesting these mutant mimics may have enhanced therapeutic potential compared to wild type (WT) miR-506-3p mimic. The objectives of my project are: 1) to compare the effect of these mutant mimics on neuroblastoma cell differentiation to that of WT mimic by measuring neurite outgrowth, a morphological differentiation marker, in neuroblastoma cells, and 2) to compare the effect of these mutants on cell growth arrest to that of WT mimic using MTT cell viability assay. This study will help to determine whether the mutant miR-506-3p mimics have higher therapeutic potential to treat neuroblastoma and widen efforts to develop more targeted therapies for high-risk patients.