MicroRNA let-7a suppresses the growth and invasion of cholesteatoma keratinocytes

Cholesteatomas are benign epidermally-derived lesions of the temporal bone that are caused by migration of hyperproliferative keratinocytes into the middle ear and mastoid cavity. The molecular mechanisms that regulate the pathogenesis of cholesteatomas are currently not fully understood. The present study demonstrated the antigrowth and anti-invasive effects of let-7a microRNA (miRNA) on cholesteatoma keratinocytes. Let-7a inhibited the growth of cholesteatoma keratinocytes through two different mechanisms: Restriction of the proliferation of keratinocytes by promoting cell cycle arrest in the G0/G1 phase, and the induction of apoptosis of the cells.. In addition to its role in the inhibition of cell growth, let-7a suppressed the migration and invasion of cholesteatoma keratinocytes. A mechanistic study showed that let-7a downregulated the expression of miR-21. Considering the function of miR-21 in the regulation of proliferation and apoptosis, let-7a may control cell proliferation and apoptosis by regulating miR-21, and its targets, in cholesteatoma keratinocyte.s. In conclusion, the present study showed that let-7a downregulates the expression of miR-21, resulting in the suppression of proliferation and induction of apoptosis. The results of the present study reveal the crucial role of let-7a miRNA in the inhibition of growth and invasion of cholesteatoma keratinocytes.