miR-25 alleviates polyQ-mediated cytotoxicity by silencing ATXN3

MicroRNAs (miRNAs) have been reported to play significant roles in the pathogenesis of various polyQ diseases. This study aims to investigate the regulation of ATXN3 gene expression by miRNA. We found that miR-25 reduced both wild-type and polyQ-expanded mutant ataxin-3 protein levels by interacting with the 3′UTR of ATXN3 mRNA. miR-25 also increased cell viability, decreased early apoptosis, and downregulated the accumulation of mutant ataxin-3 protein aggregates in SCA3/MJD cells. These novel results shed light on the potential role of miR-25 in the pathogenesis of SCA3/MJD, and provide a possible therapeutic intervention for this disorder.