Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Department of Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas.
Otol Neurotol. 2021 Sep 1;42(8):e1125-e1133. doi: 10.1097/MAO.0000000000003182.
MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph.
Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels.
Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients' preoperative pure-tone average.
Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients.
Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.
可在人类外淋巴液中发现预测可调节神经营养因子信号的 microRNAs。
动物和人类颞骨研究表明，螺旋神经节的健康状况会影响人工耳蜗植入（CI）的效果。神经营养因子已被确定为维持螺旋神经节健康的关键因素。miRNAs 的变化可能调节神经营养因子信号，并可能反映神经营养因子的表达水平。
在 18 例行耳蜗植入或镫骨切开术的患者中进行外淋巴液采样。使用 Agilent miRNA 基因芯片评估外淋巴液中 microRNA 的表达。使用 IPA 软件注释了存在于耳蜗 cDNA 文库中的靶向神经营养因子信号通路基因的 microRNAs。将外淋巴液中 microRNA 的表达水平与患者术前纯音平均听阈相关联。
在颅底手术中从正常人类耳蜗组织中鉴定出编码神经营养因子及其受体的 mRNAs 的表达。我们鉴定出了预测可调节这些信号通路的 microRNAs，包括 miR-1207-5p、miR-4651、miR-103-3p、miR-100-5p、miR-221-3p、miR-200-3p。术前听力较差与 miR-1207（预测可调节 NTR3）和 miR-4651（预测可调节 NTR2）表达水平较低相关。此外，miR-3960、miR-4481 和 miR-675 在比较轻度和重度听力损失患者时表达水平存在显著差异。
在耳蜗植入患者的外淋巴液中，一些预测可调节神经营养因子信号的 microRNAs 的表达随患者残留听力的变化而变化。这些 microRNAs 可能作为神经营养因子信号变化的生物标志物。
