miR‑142‑3p targets AC9 to regulate sciatic nerve injury‑induced neuropathic pain by regulating the cAMP/AMPK signalling pathway

Li,Xiao; Wang,Shoupeng; Yang,Xiaoli; Chu,Hongjun

doi:10.3892/ijmm.2020.4824

miR‑142‑3p targets AC9 to regulate sciatic nerve injury‑induced neuropathic pain by regulating the cAMP/AMPK signalling pathway

Authors:
- Xiao Li
- Shoupeng Wang
- Xiaoli Yang
- Hongjun Chu
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Affiliations: Department of Hand Surgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China, Department of Orthopedics, Zaozhuang Hospital of Zaozhuang Mining Group, Zaozhuang, Shandong 277100, P.R. China, Department of Pharmacy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264000, P.R. China
Published online on: December 16, 2020 https://doi.org/10.3892/ijmm.2020.4824
Pages: 561-572
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the effects of microRNA (miR)‑142‑3p on neuropathic pain caused by sciatic nerve injury in chronic compression injury (CCI) rats, and further investigate its mechanism. Rat experiments were divided into four parts in the study. In the first part, the rats were divided into the Sham and CCI groups. The expression of miR‑142‑3p, AC9 and cAMP were detected. In the second part, the rats were divided into the Sham, CCI, miR‑142‑3p mimic, mimic‑negative control (NC), miR‑142‑3p small interfering RNA (siRNA) and siRNA‑NC groups. The expression of cAMP and the levels of AMPK pathway‑related proteins were detected. In the third part, the rats were randomly divided into Sham, CCI, AC9 mimic, mi‑NC, AC9 siRNA and si‑NC groups. Double luciferase reporter assay was used to analyse the targeting relationship between miR‑142‑3p and AC9. In the fourth part, the rats were divided into the Sham, CCI, miR‑142‑3p siRNA, AC9 mimic, miR‑142‑3p siRNA + AC9 siRNA, cAMP activator (Forskolin) and miR‑142‑3p siRNA + cAMP inhibitor groups. The expression of miR‑142‑3p was significantly increased while AC9 and cAMP expression significantly decreased in CCI rats. However, AC9 overexpression significantly increased the levels of cAMP protein. Luciferase reporter assay also proved that AC9 is the target gene of miR‑142‑3p. Moreover, miR‑142‑3p silencing was found to reduce neuropathic pain in CCI rats by upregulating the expression of AC9. It was also found that cAMP activation can relieve neuropathic pain and promote the expression of AMPK‑related proteins in CCI rats. Silencing miR‑142‑3p can target AC9 to reduce the expression of inflammatory factors and neuropathic pain in CCI rats by increasing the expression of cAMP/AMPK pathway‑related proteins.

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