MicroRNA-207 enhances radiation-induced apoptosis by directly targeting Akt3 in cochlea hair cells.
MicroRNA-207 enhances radiation-induced apoptosis by directly targeting Akt3 in cochlea hair cells.
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DOI：
10.1038/cddis.2014.407
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发表时间：
2014-10-02
影响因子：
9
通讯作者：
Yuan YW
中科院分区：
文献类型：
--
作者：
Tan PX;Du SS;Ren C;Yao QW;Zheng R;Li R;Yuan YW
MicroRNAs （miRNAs）在各种类型的细胞生物学过程中发挥着重要作用。我们的研究旨在确定mirna是否在电离辐射（IR）诱导的听觉细胞死亡的调控中起作用，并确定它们如何影响细胞对IR的反应。采用芯片技术和qRT-PCR技术鉴定并确认IR后耳蜗毛细胞HEI-OC1和体内miRNAs的差异表达。使用miRNA模拟物或抑制剂检测miRNA的上调或下调，以表征所指示的miRNA的生物学效应。通过生物信息学分析、荧光素酶报告基因检测和mRNA敲除来鉴定miRNA靶基因。我们确定miR-207在IR后显著上调。MiR-207增强ir诱导的HEI-OC1细胞凋亡和DNA损伤。此外，Akt3被证实是miR-207的直接靶点。Akt3的下调类似于miR-207的作用。MiR-207通过直接靶向Akt3增强IR诱导的细胞凋亡，anti-miR-207可能在保护耳蜗毛细胞免受IR影响方面具有潜在作用。
MicroRNAs (miRNAs) have important roles in various types of cellular biological processes. Our study aimed to determine whether miRNAs function in the regulation of ionizing radiation (IR)-induced cell death in auditory cells and to determine how they affect the cellular response to IR. Microarray and qRT-PCR were performed to identify and confirm the differential expression of miRNAs in the cochlea hair cell line HEI-OC1 and in vivo after IR. Upregulation or downregulation of miRNAs using miRNA mimics or inhibitor were detected to characterize the biological effects of the indicated miRNAs. Bioinformatic analyses, luciferase reporter assays and mRNA knockdown were performed to identify a miRNA target gene. We determined that miR-207 was significantly upregulated after IR. MiR-207 enhances IR-induced apoptosis and DNA damage in HEI-OC1 cells. Furthermore, Akt3 was confirmed to be a direct target of miR-207. Downregulation of Akt3 mimics the effects of miR-207. MiR-207 enhances IR-induced apoptosis by directly targeting Akt3 and anti-miR-207 may have a potential role in protecting cochlea hair cells from IR.