Role of microRNA-375-3p-mediated regulation in tinnitus development

Abstract

Changes in the dorsal cochlear nucleus (dCN) following exposure to noise play an important role in the development of tinnitus. As the development of several diseases is known to be associated with microRNAs (miRNAs/miRs), the aim of the present study was to identify the miRNAs that may be implicated in pathogenic changes in the dCN, resulting in tinnitus. A previously developed tinnitus animal model was used for this study. The study consisted of four stages, including identification of candidate miRNAs involved in tinnitus development using miRNA microarray analysis, validation of miRNA expression using reverse transcription-quantitative PCR (RT-qPCR), evaluation of the effects of candidate miRNA overexpression on tinnitus development through injection of a candidate miRNA mimic or mimic negative control, and target prediction of candidate miRNAs using mRNA microarray analysis and western blotting. The miRNA microarray and RT-qPCR analyses revealed that miR-375-3p expression was significantly reduced in the tinnitus group compared with that in the non-tinnitus group. Additionally, miR-375-3p overexpression via injection of miR-375-3p mimic reduced the proportion of animals with persistent tinnitus. Based on mRNA microarray and western blot analyses, connective tissue growth factor (CTGF) was identified as a potential target for miR-375-3p. Thus, it was inferred that CTGF downregulation by miR-375-3p may weaken with the decrease in miRNA expression, and the increased pro.apoptotic activity of CTGF may result in more severe neuronal damage, contributing to tinnitus development. These findings are expected to contribute significantly to the development of a novel therapeutic approach to tinnitus, thereby bringing about a significant breakthrough in the treatment of this potentially debilitating condition.