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Utility of Perilymph microRNA Sampling for Identification of Active Gene Expression Pathways in Otosclerosis

Wichova, Helena; Shew, Matthew; Staecker, Hinrich

doi: 10.1097/MAO.0000000000002243
OTOSCLEROSIS
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Hypothesis: Profiling of microRNA (miRNA) within perilymph samples collected at the time of stapedectomy can be used to identify active gene expression pathways in otosclerosis as compared with controls.

Background: miRNAs are small non-coding RNAs that effect gene expression by post-transcription regulation and silencing. Perilymph sampling allows for a novel way to collect material actively involved in the disease process.

Methods: Perilymph was collected at time of stapedectomy, underwent a microarray analysis, and significantly expressed miRNAs were correlated to known bone morphology pathways using a cochlear transcriptome library. To determine miRNA related specifically to otosclerosis, cochlear implant controls were used for statistical analysis.

Results: A total of 321 significantly expressed miRNAs were identified within the four otosclerosis perilymph samples. miRNAs associated with 23 genes involved in bone morphology pathways were significantly expressed. A significant difference in the otosclerotic samples as compared with control was noted in miRNA expression regulating HMGA2, ITGB3, SMO, CCND1, TP53, TP63, and RBL2 gene pathways. No significant difference was noted in miRNAs expression associated with ACE, RELN, COL1A1, and COL1A2 genes which were previously correlated with otosclerosis.

Conclusions: Perilymph miRNA profiling obtained at the time of stapedectomy consistently identifies differentially expressed genes compared with controls. Perilymph miRNA sampling with cochlear transcriptome library cross-referencing can be successfully used to identify active gene expression pathways in otosclerosis.

Department of Otolaryngology, Head & Neck Surgery, The University of Kansas Medical Center, Kansas City, Kansas

Address correspondence and reprint requests to Helena Wichova, M.D., 3901 Rainbow Blvd MS 3010 Kansas City, KS 66160; E-mail: hwichova@kumc.edu

Funding/Financial Disclosure: None.

The authors disclose no conflicts of interest.

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