Learning Objectives:
Objective: Cholesteatoma is characterized by a extraordinary extensive bone destruction in the middle ear and mastoid cavities. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. The goal of this study was to investigate the posttranscriptional regulatory effects controlling bone destruction in cholesteatoma. Specifically, the potential role of microRNA-17 is to control osteoclasts through RANKL targeting in cholesteatoma.
Methods: Cholesteatoma, taking from patients at the time of surgery, were processed for RNA and protein extraction. Specimens of cholesteatoma and normal post-auricular auditory skin served as the control. Real-time reverse-transcription polymerase chain reaction was used to assess the expression levels of microRNA-17. Also, western blot analyses were used to assess microRNA-17's downstream target protein.
Results: MicroRNA-17 showed an down-regulation in cholesteatomas compared to normal skin. MicroRNA-17 showed 2.75 fold higher in expression in skins as compared to cholesteatomas (P = 0.019). The downstream target of miRNA-17, RANKL protein, was found to greatly increase in cholesteatomas.
Conclusions: This study specifically identified the down-regulation of miRNA-17 concurrent with the up-regulation of the receptor activator of NF-[Kappa]B ligand (RANKL), which activates osteoclasts and plays a significant role in the mechanism of bone destruction in cholesteatoma.
The results give a partial explanation for the more extensive bone destruction in the middle ear and mastoid cavities which has been observed in cholestatoma.
