Neuroblastoma is a prominent childhood cancer 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 of mRNA. Differentiation-inducing miRNA mimics, synthetic RNA molecules that imitate the mature miRNA duplexes and their functions, are potential therapeutic agents. Previous studies have shown miR-506-3p to be a strong inducer of neuroblastoma cell differentiation, suggesting the potential of applying miR-506-3p mimics to neuroblastoma differentiation therapy. The aim of my study is to investigate the cell differentiation activity of mutant miR-506-3p oligos to that of the wildtype (WT). Neurite outgrowth, a morphological differentiation marker in neuroblastoma cells, and MTT cell viability assay were used to distinguish the undifferentiated and differentiated state of neuroblastoma cells. The differentiation inducing effect of miR-506-3p mimics containing mutations along the middle and the 3’ end positions (#13-#16) was analyzed. The results indicate several mutant miR-506-3p oligos to have a comparable cell differentiation activity to that of the WT miR-506-3p. Findings provide a foundation to widen the development of novel therapeutic agents to combat neuroblastoma. Further molecular analysis is needed to determine its application in miRNA-based therapeutics for neuroblastoma patients.

Mutant miR-506-3p oligos: Promote differentiation in neuroblastoma cells

ACS Spring 2022

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