Global MicroRNA Expression Profiling Reveals Differential Expression of Target Genes in 6-Hydroxydopamine-injured MN9D Cells

Abstract

Recent evidence indicates that microRNAs (miRNAs) play a key role in neurodegenerative diseases. However, little is known about how these small RNAs contribute to dopaminergic neuronal apoptosis. Here, we profiled the expression of miRNAs in MN9D cells with and without 6-hydroxydopamine (6-OHDA) treatment by miRCURY™ LNA microRNA arrays. We identified six miRNAs (miR-668-3p, let-7d-3p, miR-3077-3p, miR-665-5p, miR-99b-3p, and miR-323-3p) that were significantly lower and five miRNAs (miR-875, miR-207, miR-425-5p, miR-19b-3p, and miR-338-3p) that were significantly higher after 6-OHDA treatment. Among them, five have been demonstrated to be implicated in neurodegenerative diseases. Consistent with our prediction, the deregulated miRNA's target mRNAs, such as peroxiredoxin III (Prx III) and Myc, also showed changes in their expression levels. Furthermore, using a dual-luciferase reporter assay, we confirmed that Prx III was a direct target gene of miR-875. Taken together, these findings demonstrate that changes in miRNA expression occur after 6-OHDA treatment and suggest that miRNAs and their predicted targets have a potential role in apoptosis of MN9D cells.