Therapeutic restoration of miR-96 prevents hearing loss in mice through modulation of noise-induced and genetic pathways

This is the authors' abstract. We don't add key points for this paper.

Hearing loss often arises from impairments in multiple genes, complicating therapeutic development. MicroRNAs, as master regulators, offer promising targets for complex diseases. We explored miR-96 's roles in hair cell (HC) function and noise-induced hearing loss (NIHL), finding that miR-96 −/− , not miR-96 +/− , mice exhibited progressive hearing loss due to gene regulatory network dysregulation from miR-96 loss in HCs not spiral ganglion neurons (SGNs). Viral-mediated delivery of miR-96 into the inner ear partially rescued hearing of miR-96 −/− mice. Tamoxifen-induced depletion of miR-96 in adult UBC CreERT2/+ ; miR-96 fl/fl mice led to hearing loss, with Bach2 , Gabra2 , Gabra4 , and Grk1 upregulation and Tnn , Col11a1 , Gjb3 , and Hnf4a downregulation. Furthermore, noise trauma reduced miR-96 , altering Bach2 , Bcl2l1 , Slc26a9 , Gabrb1 , Grk1 , Nos2 , and Cyp1a1 expression, whereas miR-96 overexpression protected hearing against noise by reversing the expression of Bach2 , Bcl2l1 , and Cyp1a1 . Our findings underscore miR-96 's essential role in adult hearing maintenance and NIHL prevention, presenting it as a promising therapeutic target.