Oncotarget

Research Papers:

miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats

Jian Wang, Wei Xu, Jiali Shao, Zhenghua He, Zhuofeng Ding, Jiangju Huang, Qulian Guo and Wangyuan Zou _

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Oncotarget. 2017; 8:28203-28214. https://doi.org/10.18632/oncotarget.15997

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Abstract

Jian Wang1, Wei Xu1, Jiali Shao1, Zhenghua He1, Zhuofeng Ding1, Jiangju Huang1, Qulian Guo1, Wangyuan Zou1

1Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China

Correspondence to:

Wangyuan Zou, email: wangyuanzou@hotmail.com

Keywords: morphine tolerance, microRNA, CaMKIIγ, NMDA

Received: August 31, 2016     Accepted: February 27, 2017     Published: March 08, 2017

ABSTRACT

Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment. Overexpression of miR-219-5p by lentivirus injection prevents the development of morphine tolerance. CaMKIIγ, the target gene of miR-219-5p was downregulated by overexpression of miR-219-5p both in vivo and in vitro. Furthermore, we found that lentiviral-mediated miR-219-5p decreased the expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine tolerance.


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