Shew Matthew, Wichova Helena, St Peter Madeleine, Warnecke Athanasia, Staecker Hinrich
Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States.
Department of Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, KS, United States.
Front Neurol. 2021 Jun 16;12:646928. doi: 10.3389/fneur.2021.646928. eCollection 2021.
Menière's disease microRNA (miRNA) profiles are unique and are reflected in the perilymph and serum of patients. Development of effective biomarkers for Menière's disease are needed. miRNAs are small RNA sequences that downregulate mRNA translation and play a significant role in a variety of disease states, ultimately making them a promising biomarker. miRNAs can be readily isolated from human inner ear perilymph and serum, and may exhibit disease-specific profiles. Perilymph sampling was performed in 10 patients undergoing surgery; 5 patients with Meniere's disease and 5 patients with otosclerosis serving as controls. miRNAs were isolated from the serum of 5 patients with bilateral Menière's disease and compared to 5 healthy age-matched controls. For evaluation of miRNAs an Agilent miRNA gene chip was used. Analysis of miRNA expression was carried out using Qlucore and Ingenuitey Pathway Analysis software. Promising miRNAs biomarkers were validated using qPCR. In the perilymph of patients with Menière's disease, we identified 16 differentially expressed miRNAs that are predicted to regulate over 220 different cochlear genes. Six miRNAs are postulated to regulate aquaporin expression and twelve miRNAs are postulated to regulate a variety of inflammatory and autoimmune pathways. When comparing perilymph with serum samples, miRNA-1299 and-1270 were differentially expressed in both the perilymph and serum of Ménière's patients compared to controls. Further analysis using qPCR confirmed miRNA-1299 is downregulated over 3-fold in Meniere's disease serum samples compared to controls. Patients with Ménière's disease exhibit distinct miRNA expression profiles within both the perilymph and serum. The altered perilymph miRNAs identified can be linked to postulated Ménière's disease pathways and may serve as biomarkers. miRNA-1299 was validated to be downregulated in both the serum and perilymph of Menière's patients.
梅尼埃病的微小RNA(miRNA)谱是独特的,且在患者的外淋巴和血清中有所体现。因此需要开发针对梅尼埃病的有效生物标志物。miRNA是下调mRNA翻译的小RNA序列,在多种疾病状态中发挥重要作用,这使其成为一种有前景的生物标志物。miRNA可以很容易地从人内耳外淋巴和血清中分离出来,并且可能呈现疾病特异性谱。对10名接受手术的患者进行了外淋巴采样;其中5例梅尼埃病患者和5例耳硬化症患者作为对照。从5例双侧梅尼埃病患者的血清中分离出miRNA,并与5例年龄匹配的健康对照进行比较。使用安捷伦miRNA基因芯片对miRNA进行评估。使用Qlucore和Ingenuity Pathway Analysis软件进行miRNA表达分析。使用qPCR对有前景的miRNA生物标志物进行验证。在梅尼埃病患者的外淋巴中,我们鉴定出16种差异表达的miRNA,预计这些miRNA可调控超过220种不同的耳蜗基因。推测有6种miRNA可调控水通道蛋白的表达,12种miRNA可调控多种炎症和自身免疫途径。当将外淋巴与血清样本进行比较时,与对照组相比,miRNA - 1299和 - 1270在梅尼埃病患者的外淋巴和血清中均有差异表达。使用qPCR进行的进一步分析证实,与对照组相比,梅尼埃病血清样本中miRNA - 1299下调超过3倍。梅尼埃病患者在外淋巴和血清中均表现出独特的miRNA表达谱。所鉴定出的外淋巴中改变的miRNA可能与推测的梅尼埃病途径相关,并可能作为生物标志物。已验证miRNA - 1299在梅尼埃病患者的血清和外淋巴中均下调。