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Review
. 2022 Jan 7;7(1):60-66.
doi: 10.1002/lio2.728. eCollection 2022 Feb.

Non-coding RNA and cholesteatoma

Ivan Jovanovic  1 , Maja Zivkovic  1 , Snezana Jesic  2   3 , Aleksandra Stankovic  1
Affiliations
Review

Non-coding RNA and cholesteatoma

Ivan Jovanovic et al. Laryngoscope Investig Otolaryngol. .

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.

Level of Evidence: NA.

Keywords: RNA interaction; cholesteatoma; long noncoding RNA; micro RNA; noncoding RNA.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Noncoding RNA interplay in regulation of the mRNA expression. The figure depicts the mechanism of gene expression regulation in the absence and presence of competing endogenous RNA (ceRNA) interactions with miRNAs. (A) In the absence of ceRNA (circRNA and lncRNA) various miRNAs incorporated in RNA‐induced silencing complex (miRISC) induce degradation or repression of translation of target mRNA; (B) When ceRNAs (circRNA and lncRNA) harboring the same miRNA response elements (MREs) as the target mRNAs are present, they complementary sequester miRISCs (green, red, or blue) and consequently lower cellular levels of free miRISCs, which leads to increased translation; Cellular levels of miRISC (orange) remains unchanged since lcnRNAs do not harbor the same MREs as the target mRNA, thus not affecting the miRNA‐mRNA regulation, which results in unchanged, miRNA‐induced target mRNA degradation, or repression of translation
FIGURE 2
FIGURE 2
The network of described ncRNA activity in cholesteatoma pathogenesis. The Network depicts interplay of ncRNAs in cholesteatoma and regulation of target genes associated with cholesteatoma pathology. Orange boxes emphasize miRNAs which are potential biomarkers and targets for miRNA therapeutics in cholesteatoma. Yellow boxes emphasize lncRNAs and circRNAs as potential regulators of miRNA actions on gene expression. Blue boxes represent target genes implicated in cholesteatoma, related to presented ncRNA interplay
See this image and copyright information in PMC

References

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