Novel miRNAs, miR-937-3p, miR-4536-3p, and miR-4650-5p, can Modulate Neuronal Differentiation via the Wnt/MAPK Pathway in SH-SY5Y Cells

MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes, including cell differentiation. Despite their potential, their role in promoting neuronal differentiation by targeting neuronal genes and modulating signaling pathways is poorly understood. In this study, we aimed to elucidate the functions of miR-937-3p-, miR-4536-3p-, and miR-4650-5p-inhibitors in the neuronal differentiation of SH-SY5Y cells. We also aimed to determine the underlying mechanisms via qPCR, luciferase assay, immunocytochemistry, and western blotting analysis. Our findings confirmed that miRNAs participated in neuronal differentiation and regulated the Wnt/MAPK signaling pathway. Specifically, we identified Netrin1 (NTN1), Drebrin1 (DBN1), and Netrin-G1 (NTNG1) as target genes of miR-937-3p, miR-4536-3p, and miR-4650-5p, respectively. The treatment with the miRNA inhibitors increased the expression levels of neuronal markers such as TUBB3, NEFH, NEFM, NEFL, and MAP2. It also enhanced the protein expression levels of Wnt and MAPK signaling. Therefore, the inhibitors of miR-937-3p, miR-4536-3p, and miR-4650-5p could promote neuronal differentiation by targeting neuronal genes and activating the Wnt/MAPK signaling pathway.