Chen Z B, Pu M M, Yao J, Cao X, Cheng L
Department of Otorhinolaryngology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Nov 7;53(11):830-837. doi: 10.3760/cma.j.issn.1673-0860.2018.11.007.
To screen the key microRNAs targeting Notch signaling pathway in inner ear and investigate its potential regulating function. The interaction network and the Core-Notch network, involved with key genes in Notch signal pathway and differential-expressed microRNAs in inner ear, were constructed by bioinformatics methods. The important microRNAs in regulating Notch signaling pathway were screened via topological and GO analysis, followed by and investigation. MiRNA-384-5p was identified as a key regulator specifically expressed in mouse brain and inner ear, which could down-regulate . The expression was found significantly down-regulated in miRNA-384-5p-mimic-transfected HeLa cells. The dual-luciferase reporter gene assay further confirmed the effect of miRNA-384-5p on the down-regulation of and in Notch signaling pathway. The Core-Notch network is constructed to screen microRNAs implicated in inner ear development, and miRNA-384-5p is screened and verified to be target-regulating the Notch signaling pathway, which could be the potential target in the regeneration of impaired hair cells.
筛选内耳中靶向Notch信号通路的关键微小RNA,并研究其潜在调控功能。采用生物信息学方法构建了与Notch信号通路关键基因及内耳差异表达微小RNA相关的相互作用网络和核心Notch网络。通过拓扑学和基因本体(GO)分析筛选出调控Notch信号通路的重要微小RNA,随后进行研究。miRNA-384-5p被鉴定为在小鼠脑和内耳中特异性表达的关键调节因子,其可下调……。在转染了miRNA-384-5p模拟物的HeLa细胞中发现……表达显著下调。双荧光素酶报告基因检测进一步证实了miRNA-384-5p对Notch信号通路中……和……下调的作用。构建核心Notch网络以筛选参与内耳发育的微小RNA,筛选并验证了miRNA-384-5p可靶向调控Notch信号通路,其可能是受损毛细胞再生的潜在靶点。