MiR-183 family regulates chloride intracellular channel 5 expression in inner ear hair cells
MiR-183 family regulates chloride intracellular channel 5 expression in inner ear hair cells
复制标题
MiR-183 家族调节内耳毛细胞中氯离子通道 5 的表达。
DOI：
10.1016/j.tiv.2012.07.008
复制
发表时间：
2013-02-01
影响因子：
3.2
通讯作者：
Liu, Yimin
中科院分区：
文献类型：
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作者：
Gu, Chunhui;Li, Xudong;Liu, Yimin
MiRNAs在听力和耳聋发病中的作用开始被揭示。尽管到目前为止还没有报道氯离子细胞内通道5(CLIC5)与miR-183家族之间的联系，但我们在这里提出的证据表明，它们在内耳中共同表达，并具有与立体纤毛相关的功能。此外，CLIC5在其3‘-UTR中含有一个预测的高度保守的miR-96/-182结合位点。我们目前的结果进一步表明，miR-96/-182和CLIC5在HEI-OC1细胞中共表达，其中存在两种不同的CLIC5蛋白。此外，还发现miR-96和miR-182在脂质体介导的HEI-OC1细胞中特异性过表达，导致CLIC5在mRNA和蛋白水平下调。最后，miR-96/-182特异性地下调荧光素酶报告基因的表达，该报告基因被克隆到含有野生型miR-96/-182靶序列的小鼠CLIC5 3‘-UTR片段中。因此，我们的发现表明CLIC5直接受miR-96和miR-182调控，这方面的靶序列位于CLIC5 3‘-UTR内的760-766核苷酸之间。(C)2012爱思唯尔有限公司。保留所有权利。
The roles of miRNAs in the onset of hearing and deafness are beginning to be revealed. Although there has been no reported link between chloride intracellular channel 5 (CLIC5) and the miR-183 family to date, we here present evidence that they are co-expressed in the inner ear and have functions that are related to stereocilia. Moreover, CLIC5 contains a single predicted and highly conserved miR-96/-182 binding site within its 3'-UTR. Our current results further show that miR-96/-182 and CLIC5 are co-expressed in HEI-OC1 cells, in which two isoforms of the CLIC5 protein exist. Furthermore, miR-96 and miR-182 were found to be specifically overexpressed in HEI-OC1 cells into which mimics of these molecules had been transfected by liposomes causing the downregulation of CLIC5 at both the mRNA and protein levels. Finally, miR-96/-182 specifically downregulate the expression of the luciferase reporter gene which was cloned into a mouse CLIC5 3'-UTR fragment containing the wild-type miR-96/-182 target sequence. Our findings thus suggest that CLIC5 is directly regulated by miR-96 and miR-182 and that the target sequence in this regard is located between nucleotides 760-766 within the CLIC5 3'-UTR. (C) 2012 Elsevier Ltd. All rights reserved.