miR-9 and miR-218 modulate α7 nicotinic acetylcholine receptors levels via targeting of RIC-3 chaperone

Abstract

Abstract Nicotinic acetylcholine receptors (nAChRs) have a role in a variety of pathophysiological conditions. Resistant to inhibitor cholinesterase (RIC-3) is a chaperone protein responsible for proper folding and assembly of α7 subunit of nAChRs. A variety of microRNAs, including miR-9 and miR-218, affect RIC-3. Thus, in the current study, the targeting of the RIC-3 gene with miR-9 and miR-218 was investigated. HEK-293 cells were transfected with miR-9 and miR-218 pre-mature miRNAs and were subjected to qRT-PCR, luciferase assay, and western blotting. The obtained results revealed that exogenous upregulation of miR-9/miR-218 further reduced RIC-3 mRNA and protein expression. In addition, luciferase assay illustrated that miR-9/miR-218 directly binds to the specific regions in RIC-3 3’-UTR and suppresses its expression. Also, it was found that miR-9/miR-218 mediated suppression of RIC-3 led to significant decreases of α7nAChR at protein levels. In conclusion, our findings implied that miR-9 and miR-218 might be involved in the receptor related-cellular signaling through modulating the RIC-3/α7 nAChR axis.