Downregulation of lncRNA FIRRE relieved the neuropathic pain of female mice by suppressing HMGB1 expression

• Published in: Molecular and cellular biochemistry 2021-02, Vol.476 (2), p.841-852
• Main Authors: Wen, Yuanyuan, Fan, Xiaochong, Bu, Huilian, Ma, Letian, Kong, Cunlong, Huang, Chen, Xu, Yuming
• Format: Article
• Language: English
• Subjects: Analysis; Biochemistry; Biomedical and Life Sciences; Cardiology; Care and treatment; Chromosomal proteins; Cytokines; Gene expression; HMGB1 protein; IL-1β; Immunoprecipitation; Inflammation; Interleukin 6; Life Sciences; Lipopolysaccharides; Medical Biochemistry; Methyl salicylate; Microglia; Mitogens; Neuralgia; Non-coding RNA; Oncology; Overexpression; Pain; Ribonucleic acid; RNA; Rodents; Silence; Spinal cord; Surgery; Tumor necrosis factor-α; Ubiquitination
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03949-7

Long non-coding RNAs are novel regulators in neuropathic pain. In this study, we aimed to explore the role and the mechanism of lncRNA FIRRE in regulating the secretion of microglial cells-derived proinflammatory cytokines in neuropathic pain. The female mouse model of neuropathic pain was established by bilateral chronic constriction injury (CCI) surgery. The mouse primary microglial cells were induced by lipopolysaccharide (LPS). The interaction between FIRRE and high mobility group box 1 (HMGB1) was assessed by RNA immunoprecipitation, RNA pull-down, and ubiquitination assays. FIRRE expression was upregulated in the spinal cord tissue of female CCI mice and LPS-induced microglial cells. The concentrations of IL-1β, TNF-α, and IL-6 from LPS-induced microglial cells were reduced by FIRRE knockdown. FIRRE bound to HMGB1 and negatively regulated its protein level. The ubiquitination degradation of HMGB1 was promoted by FIRRE silence. The HMGB1 over-expression reversed the inhibitory effect of FIRRE silence on the secretion of IL-1β, TNF-α, and IL-6 from LPS-induced microglial cells. The in vivo experiment showed that FIRRE knockdown alleviated neuropathic pain of CCI female mice. Our findings indicated that lncRNA FIRRE downregulation inhibits the secretion of microglial cells-derived proinflammatory cytokines by decreasing HMGB1 expression, thereby relieving neuropathic pain of female mice.