Non‐coding RNA and cholesteatoma

Abstract

Objective: Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding RNAs (ncRNA) as a new class of regulatory molecules. Methods:We have comprehensively reviewed all articles investigating ncRNAs, specifically micro RNAs (miRNAs) and long ncRNAs (lncRNA/circRNA) in cholesteatoma tissue.Results: Candidate miRNA approaches indicated that miR-21 and let-7a are the major miRNAs involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncRNAs implicated in cholesteatoma pathology. Competitive endogenous RNA (ceRNA) analysis highlighted lncRNA/circRNA that could be "endogenous sponge" for miR-21 and let-7a based on the hypothesis that RNA transcripts can communicate with and regulate each other by using shared miRNA response elements. Conclusion:In this review, we summarize the discoveries and role of ncRNA in major pathways in cholesteatoma and highlight the potential of miRNA-based therapeutics in the treatment of cholesteatoma.

Identification of miRNA expression profile in middle ear cholesteatoma using small RNA-sequencing

“…Middle ear cholesteatoma is a relatively common disease in otolaryngology [ 20 ], the pathogenesis and mechanisms of which have been drawing growing attention. Numerous studies revealed the roles of miRNAs in the formation and progression of cholesteatoma [ 9 , 10 ].In the present study, we identified 121 significantly differentially expressed miRNAs in acquired retraction pocket cholesteatoma tissues via small RNA sequencing. Among them, 56 miRNAs were upregulated, and 65 miRNAs were downregulated.…”

“…Several research suggested the genetic associations of cholesteatoma in syndromic and familial forms [7,8]. Also, researchers have recently paid attention to the role of non-coding RNAs in cholesteatoma pathogenesis which have certain therapeutic potential [9,10]. Complete removal of the lesion, preservation of normal middle ear mucosa, and restoration of the middle ear ventilation and drainage system during surgery help reduce the recurrence of cholesteatoma [11][12][13].…”

A micro-computed tomography study of the sinus tympani variation in humans

“…Although cholesteatoma has been recognized for more than three centuries [20], the nature of this disorder has yet not been fully determined, particularly the factors regulating its progression [28]. Some studies revealed that sex predilection for cholesteatoma might be dependent on the expression of female sex hormone receptors in the middle ear that act as an auditory protectant [43].…”