Comparative transcriptome analysis of auditory OC-1 cells and zebrafish inner ear tissues in the absence of human OSBPL2 orthologues.

In our previous study, Oxysterol-binding protein-related protein 2 (OSBPL2) was first identified as a new deafness-causative gene contribute to non-syndromic hearing loss. However, the underlying mechanism of OSBPL2-induced hearing loss remains unknown. Here, we used hearing-specific cells and tissues OC-1 cells and zebrafish inner ear tissues as models to identify common transcriptome changes in genes and pathways in the absence of human OSBPL2 orthologues by RNA-seq analysis. In total, 2112 differentially expressed genes (DEGs) were identified between wild-type (WT) and Osbpl2^-/- OC-1 cells, and 877 DEGs were identified between WT and osbpl2b^-/- zebrafish inner ear tissues. Functional annotation implicated Osbpl2/osbpl2b in lipid metabolism, cell adhesion and the extracellular matrix in both OC-1 cells and zebrafish inner ear tissues. Protein-protein interaction (PPI) analysis indicated that Osbpl2/osbpl2b were also involved in ubiquitination. Further experiments showed that Osbpl2^-/- OC-1 cells exhibited an abnormal focal adhesion morphology characterized by inhibited FAK activity and impaired cell adhesion. In conclusion, we identified novel pathways modulated by OSBPL2 orthologues, providing new insight into the mechanism of hearing loss induced by OSBPL2 deficiency.

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