Abstract
BackgroundMiddle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. Circular RNA (circRNA) plays an essential role in the pathogenesis of many proliferative diseases. However, the role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. We aimed to investigate the differential expression profiling of circRNAs between acquired middle ear cholesteatoma and normal skin, and to identify potential circRNAs contributing to the etiopathogenesis of middle ear cholesteatoma. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Validation of differentially expressed circRNAs was conducted by qRT-PCR. Prediction of m6A modification was also carried out.ResultsMicroarray analysis displayed that totally 93 up-regulated and 85 down-regulated circRNAs were identified in middle ear cholesteatoma. Through validation, expressions of hsa_circRNA_104327 and hsa_circRNA_404655 were significantly higher, while hsa_circRNA_000319 was significantly down-regulated in cholesteatoma. GO classification, KEGG pathway, and ceRNA network analyses suggested that these differentially expressed circRNAs might play important roles in the etiopathogenesis of middle ear cholesteatoma. Prediction of m6A modification exhibited that hsa_circRNA_000319 possessed 4 m6A sites with very high confidence, and hsa_circRNA_404655 had 3 m6A sites with high confidence.ConclusionsOur study revealed that these differentially expressed circRNAs might contribute to the etiopathogenesis of middle ear cholesteatoma. Further researches should be conducted to investigate the exact mechanism of these differentially expressed circRNAs in the etiopathogenesis of middle ear cholesteatoma. Targeting on these circRNAs may provide a new strategy for middle ear cholesteatoma therapy in the future.
Highlights
Middle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes
Differential expressions of Circular RNA (circRNA) in cholesteatoma and normal skin In our study, a total of 13,562 expressed circRNAs were detected through microarray analysis
The differentially expressed circRNAs were displayed in a volcano plot (Fig. 1A), and subjected to a scatter plot (Fig. 1B) and hierarchical clustering analysis (Fig. 1C), to display the variation and differentiation between middle ear cholesteatoma and normal skin
Summary
Middle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. The role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Middle ear cholesteatoma is a locally destructive squamous epithelial lesion with clinical features such as hyper-proliferation, migration, aggressiveness, and recurrence. A wide spectrum of hypotheses have been put forward, the exact etiopathogenesis of middle ear cholesteatoma is not clear yet. Since there is no effective drug for treating middle ear cholesteatoma, surgical resection is still the only option presently. Surgical resection is often accompanied by dysfunction of middle and inner ear, which may cause further hearing loss [4]. For patients with poor general conditions, such as severe respiratory diseases, cardiovascular and cerebrovascular diseases, surgical resection cannot be performed
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