MiR‑142‑3p Targets AC9 to Regulate Sciatic Nerve Injury‑induced Neuropathic Pain by Regulating the CAMP/AMPK Signalling Pathway

Overview

Journal Int J Mol Med

Specialty Genetics

Date 2021 Jan 8

PMID 33416140

Citations 10

Authors

Xiao Li

Shoupeng Wang

Xiaoli Yang

Hongjun Chu

Affiliations

Soon will be listed here.

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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