MiR-181a is a negative regulator of GRIA2 in methamphetamine-use disorder

Abstract

A previous study reported that the miR-181a level in serum was significantly different between patients with methamphetamine-use disorder and healthy controls and that chronic methamphetamine use down-regulates the expression of miR-181a. Bioinformatic analysis predicted that miR-181a might bind the 3′-UTRs of the mRNA transcripts of the human glutamate receptor genes GRIA2 and GABRA1. In this study, we measured the expression of GRIA2 and GABRA1 in patients with methamphetamine-use disorder. In addition, we examined whether miR-181a down-regulates GRIA2 and GABRA1 in a cell-based assay. We further examined the effects of chronic methamphetamine exposure on the expression of miR-181a, GRIA2 and GABRA1. The results demonstrated that serum GRIA2 is higher in patients with methamphetamine-use disorder than in healthy controls. Dual luciferase reporter assays and a cell-based model of methamphetamine exposure also showed that miR-181a directly regulates expression of GRIA2. This study supports the evidence that miR-181a and the glutamate AMPA receptor gene GRIA2 play a critical role in methamphetamine-use disorder.