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

Jian Wang, Wei Xu, Tao Zhong, Zongbin Song, Yu Zou, Zhuofeng Ding, Qulian Guo, Xinzhong Dong, Wangyuan Zou

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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.

Original languageEnglish (US)
Article number38285
JournalScientific Reports
StatePublished - Dec 6 2016


ASJC Scopus subject areas

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Cite this

Wang, J., Xu, W., Zhong, T., Song, Z., Zou, Y., Ding, Z., Guo, Q., Dong, X., & Zou, W. (2016). MiR-365 targets β-arrestin 2 to reverse morphine tolerance in rats. Scientific Reports, 6, [38285]. https://doi.org/10.1038/srep38285