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RNA-seq analysis of potential lncRNAs for age-related hearing loss in a mouse model

机译:小鼠模型中与年龄相关的听力损失的潜在lncRNA的RNA-seq分析

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摘要

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.
机译:与年龄有关的听力损失(AHL)是老年人口中的重要健康问题。其分子机制尚未完全阐明。在这项研究中,我们通过RNA序列分析分析了六周龄和一岁C57BL / 6J小鼠耳蜗中lncRNA和mRNA的差异表达。我们在这两组中分别发现了738和2033个差异表达的lncRNA和mRNA(校正后的<0.05)。我们专注于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。在这个交叉路口中有34个mRNA,其中包括在声音的感官感知中富集的所有29个mRNA(GO:0007605)。我们选择了11种lncRNA,它们有望通过qRT-PCR调节34种mRNA,以验证其在AHL动物和细胞模型中的表达水平。在这些lncRNA中,在AHL的动物模型和细胞模型中,有四个显着不同,而lncRNA NONMMUT010961.2的差异最为明显。敲低lncRNA NONMMUT010961.2,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着降低。我们的结果表明,lncRNA NONMMUT010961.2可能与AHL相关,因此可能导致AHL的新治疗方法。

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