Conclusions
MEG3 aggravates NP and astrocyte activation via the miR-130a-5p/CXCL12/CXCR4 axis, which is a potential therapeutic target for NP.
Methods
The chronic constriction injury (CCI) method was employed to construct an NP rat model. Astrocyte activation was induced by lipopolysaccharide (LPS). The profiles of MEG3, microRNA (miR)-130a-5p, CXC motif chemokine receptor 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4), and the Rac1/NF-κB pathway in CCI rats' spinal cord tissues and astrocytes were monitored by reverse transcription-quantitative PCR (RT-qPCR) and western blot (WB). Pain scores of CCI rats were assessed. Enzyme-linked immunosorbent assay (ELISA) was adopted to monitor neuroinflammation alteration. The glial fibrillary acidic protein (GFAP)-labeled astrocytes were tested by immunohistochemistry (IHC). Bioinformatics, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were utilized to verify the molecular mechanism between MEG3 and miR-130a-3p.
Objective
Long non-coding RNAs (lncRNAs) exert a critical function in mediating neuropathic pain (NP). MEG3, a novel lncRNA, contributes to astrocyte activation and inflammation. However, its role in NP remains unclear.
Results
MEG3, CXCL12 and CXCR4 were overexpressed and miR-130a-5p was knocked down in CCI rats and LPS-induced astrocytes. Up-regulating MEG3 aggravated NP, enhanced inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6) expression and release in CCI rats and LPS-induced astrocytes. Up-regulating miR-130-5p repressed LPS-induced inflammation in astrocytes. AS verified by the dual-luciferase reporter assay and RIP assay, MEG3 sponged miR-130a-5p as a competitive endogenous RNA (ceRNA). What's more, miR-130a-5p up-regulation weakened the MEG3-induced proinflammatory effects on LPS-induced astrocytes. Conclusions: MEG3 aggravates NP and astrocyte activation via the miR-130a-5p/CXCL12/CXCR4 axis, which is a potential therapeutic target for NP.