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

Abstract

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 keratinocytes. 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.

A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures

“…Mir-let7e play an important role in cellular proliferation, apoptosis, and inflammation by modulating the NF-κB signaling [68].…”

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

“…Apoptosis was found in the suprabasal layers of cholesteatoma epithelium but not found in the basal layers [125-127]. A recent study showed that let 7a microRNA had a vital role in the in the inhibition of growth and invasion of cholesteatoma keratinocytes via downregulation of miR 21 expression, resulting in the suppression of proliferation and induction of apoptotic activity [128]. These results might pave the way for exploring non-surgical options for cholesteatoma management.…”

“…In addition, molecules targeted to suppress proliferation and induce apoptotic activity like let 7a microRNA which was proved to have a vital role in the inhibition of growth and invasion of cholesteatoma keratinocytes via downregulation of miR 21 expression can be used in the future treatment of cholesteatoma [128]. Moreover, drugs used for inhibition of osteoclastogenesis might be of great value in cholesteatoma management [130].…”

Acquired cholesteatoma epithelial hyperproliferation: Roles of cell proliferation signal pathways

“…Because acquired middle ear cholesteatoma is characterized with hyperproliferation of epithelial cells, the role of miRNA‐21 in the cell proliferation process of cholesteatoma has become a hot issue in recent years . Friedland et al first described the potential role of miRNAs in regulating growth and proliferation in adult‐acquired cholesteatoma, identifying increased levels of miRNA‐21 concurrent with decreased PTEN and PDCD4 in cholesteatoma compared to normal postauricular skin .…”