Abstract

BackgroundEarly diagnosis of immune-related hearing loss and timely treatment can prevent structural damage to the inner ear and contribute to hearing retention. Exosomal miRNAs, lncRNAs and proteins have great prospects as novel biomarkers for clinical diagnosis. Our study aimed to investigate the molecular mechanisms of exosomes or exosomal ceRNA regulatory networks in immune-related hearing loss. MethodsAn immune-related hearing loss mice model was constructed by injection with inner ear antigen, and then the blood plasma samples of the mice were collected for exosomes isolation by ultra-centrifugation. Subsequently, the different exosomes were sent for whole transcriptome sequencing using Illumina platform. Finally, a ceRNA pair was chosen for validation by RT-qPCR and dual luciferase reporter gene assay. ResultsThe exosomes were successfully extracted from the blood samples of the control and the immune-related hearing loss mice. After sequencing, 94 differentially expressed (DE) lncRNAs, 612 DEmRNAs, and 100 DEmiRNAs were found in the immune-related hearing loss-associated exosomes. Afterwards, ceRNA regulatory networks consisting of 74 lncRNAs, 28 miRNAs and 256 mRNAs were proposed, and the genes in the ceRNA regulatory networks were significantly enriched in 34 GO terms of biological processes and 9 KEGG pathways. Finally, Gm9866 and Dusp7 were significantly up-regulated, while miR-185-5p level was declined in the exosomes from immune-related hearing loss, and Gm9866, miR-185-5p and Dusp7 interacted with each other. ConclusionsGm9866-miR-185-5p-Dusp7 was confirmed to be closely correlated with the occurrence and progression of immune-related hearing loss.

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