Hearing and Speech Rehabilitation Institute, Binzhou Medical University, Yantai, China.
Clinical Medicine Laboratory, Binzhou Medical University Hospital, Binzhou, China.
Aging (Albany NY). 2020 Apr 26;12(8):7491-7510. doi: 10.18632/aging.103103.
Age-related hearing loss (AHL) is an important health problem in the elderly population. Its molecular mechanisms have not been fully elucidated. In this study, we analyzed the differential expression of lncRNAs and mRNAs in the cochleae of six-week-old and one-year-old C57BL/6J mice through RNA-seq analysis. We found 738 and 2033 differentially expressed lncRNAs and mRNAs, respectively, in these two groups (corrected < 0.05). We focused on the intersection of known genes associated with hearing loss and differentially expressed mRNAs in RNA-seq. There are 34 mRNAs in this intersection, which include all 29 mRNAs enriched in the sensory perception of sound (GO: 0007605). We selected 11 lncRNAs that are predicted to regulate the 34 mRNAs to validate their expression levels in animal and cellular models of AHL by qRT-PCR. Among these lncRNAs, four were significantly different in both animal and cellular models of AHL, and the lncRNA NONMMUT010961.2 was the most markedly different. Knocking down lncRNA NONMMUT010961.2, we found the expression of oxidative stress and apoptosis-related gene and hearing loss-related gene is significantly reduced in HEI-OC1 cells. Our results suggest that lncRNAs NONMMUT010961.2 may be associated with AHL and may thus lead to a new treatment for AHL.
年龄相关性听力损失(AHL)是老年人群中的一个重要健康问题。但其分子机制尚未完全阐明。在本研究中,我们通过 RNA-seq 分析比较了 6 周龄和 1 岁 C57BL/6J 小鼠耳蜗中的 lncRNA 和 mRNA 的差异表达。我们分别在这两组中发现了 738 个和 2033 个差异表达的 lncRNA 和 mRNA(校正后 < 0.05)。我们重点关注与听力损失相关的已知基因和 RNA-seq 中差异表达的 mRNA 的交集。在这个交集中有 34 个 mRNA,包括在声音感觉感知(GO:0007605)中富集的所有 29 个 mRNA。我们选择了 11 个预测可以调控 34 个 mRNA 的 lncRNA,并通过 qRT-PCR 在 AHL 的动物和细胞模型中验证它们的表达水平。在这些 lncRNA 中,有 4 个在 AHL 的动物和细胞模型中均有显著差异,其中 lncRNA NONMMUT010961.2 差异最显著。敲低 lncRNA NONMMUT010961.2 后,我们发现 HEI-OC1 细胞中氧化应激和凋亡相关基因和听力损失相关基因的表达显著降低。我们的结果表明,lncRNA NONMMUT010961.2 可能与 AHL 相关,因此可能为 AHL 的治疗提供新的思路。