miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats.

miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats.
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miR-365 靶向 β-arrestin 2 以逆转大鼠吗啡耐受

DOI:
10.1038/srep38285
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发表时间:
2016-12-06
期刊:
影响因子:
4.6
通讯作者:
Zou W
Zou W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang J;Xu W;Zhong T;Song Z;Zou Y;Ding Z;Guo Q;Dong X;Zou W

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Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. Non-coding microRNAs (miRNAs) modulate gene expression in a post transcriptional manner, and their dysregulation causes various diseases. However, the significance of miRNAs in morphine tolerance is still poorly understood. In the present study, we hypothesized that microRNA-365 (miR-365) is a key functional small RNA that reverses morphine tolerance through regulation of β-arrestin 2 in rats. Here, microarray analysis and quantitative real-time PCR showed that miR-365 was robustly decreased in the spinal cord after chronic morphine administration. In situ hybridization and immunochemistry double staining showed that miR-365 was expressed in neurons of the spinal cord. We identified β-arrestin 2 as the target gene of miR-365 by bioinformatics analysis and luciferase reporter assay. The data showed that overexpression of miR-365 prevented and reversed established morphine tolerance, and increased expression of miR-365 caused a decrease in expression of β-arrestin 2 protein. miR-365 downregulation is involved in the development and maintenance of morphine tolerance through regulation of β-arrestin 2, and miR-365 upregulation provides a promising and novel approach for treatment of morphine tolerance.
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发表时间: 2010-07-28
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
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