MiR-29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1α signaling: Implications for age-related hearing loss

Abstract

It has been reported that the degeneration of cochlear hair cells is the typical cause of presbycusis (or age-related hearing loss). However, the molecular mechanisms that mediate cochlear hair cell apoptosis are not yet fully understood and there is no effective treatment for this disorder. MicroRNAs (miRNAs or miRs) have been increasingly shown to be associated with age-related diseases and are emerging as promising therapeutic targets. In this study, we investigated whether miR-29b is involved in the degeneration of cochlear hair cells. To examine our hypothesis, nuclear staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) were used to quantify the hair cell counts. RT-qPCR and western blot analysis were used to examine miR-29b/sirtuin 1 (SIRT1)/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in cochlear hair cells. We found that there was a significant degeneration of cochlear hair cells and a higher expression of miR-29b in aged C57BL/6 mice compared with young mice. There was also an age-related decrease in the expression of SIRT1 and PGC-1α. In the inner ear cell line, HEI-OC1, miR-29b overexpression (by transfection with miR-29b mimic) inhibited SIRT1 and PGC-1α expression, leading to an increase in mitochondrial dysfunction and apoptosis. Moreover, the inhibition of miR-29b (by transfection with miR-29b inhibitor) increased SIRT1 and PGC-1α expression, while it decreased apoptosis. Taken together, our findings support a link between age-related cochlear hair cell apoptosis and miR-29b/SIRT1/PGC-1α signaling, which may present an attractive pharmacological target for the development of novel drugs for the treatment of age-related hearing loss.