MiR-139-5p modulates cortical neuronal migration by targeting Lis1 in a rat model of focal cortical dysplasia

Abstract

Accumulating evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the developing rat brain. In this study, we investigated the role of miRNAs in the brains of immature (20–80 days) rats with liquid nitrogen lesion-induced focal cortical dysplasia. miRNA microarray demonstrated that the expression of miR-139-5p was associated with cortical development. Bioinformatic analysis and luciferase assays revealed that the Lis1 gene is a likely target of miR-139-5p. It is known that Lis1 plays a role in cell proliferation and migration and can lead to cortical dysplasia when mutated. Our data demonstrated an inhibitory effect of miR-139-5p on the expression of Lis1 in PC12 cells 24 h following transfection with pre-miR-139-5p. However, when the PC12 cells were transfected with anti-miR-139-5p, an increase was observed in the expression of Lis1. Cell migration assay revealed that miR-139-5p significantly inhibited the migration of PC12 and HCN-2 cells treated with or without Lis1 protein. In addition, a rat model of focal cortical dysplasia was established, wherein miR-139-5p was administered and Lis1 expression was found to be markedly reduced. Moreover, the injured cortex showed a certain degree of recovery following the administration of miR-139-5p, demonstrating that the reduction in miR-139-5p was at least partially responsible for the upregulation of Lis1 in the rat brains. Our data suggest that miR-139-5p modulates cortical neuronal migration by targeting Lis1.