title: MicroRNA-93 alleviates neuropathic pain through targeting signal transducer and activator of transcription 3.
abstract: Emerging evidence suggests that microRNAs (miRNAs) play a critical role in the pathogenesis of neuropathic pain. However, the exact role of miRNAs in regulating neuropathic pain remains largely unknown. In this study, we aimed to investigate the potential role of miR-93 in a rat model of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). We found a significant decrease of miR-93 in the spinal cord of CCI rats compared with sham rats. Overexpression of miR-93 significantly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in CCI rats. By bioinformatic analysis and dual-luciferase reporter assay, we found that miR-93 directly targeted the 3'-untranslated region (UTR) of signal transducer and activator of transcription 3 (STAT3), an important regulator of inflammation. Overexpression of miR-93 markedly suppressed the expression of STAT3 in vitro and in vivo. Furthermore, overexpression of STAT3 significantly reversed the miR-93 overexpression-induced suppressive effects on neuropathic pain development and neuroinflammation. Taken together, our study suggests that miR-93 inhibits neuropathic pain development of CCI rats possibly through inhibiting STAT3-mediated neuroinflammation. Our findings indicate that miR-93 may serve as a novel therapeutic target for neuropathic pain intervention.
authors.affiliation: Department of Anesthesiology, Shenzhen Bao'an Maternity and Child Health Hospital, Shenzhen, 518100, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Yan
authors.affiliation: Department of Sport Medicine and Pain Clinic, Center of Sports Rehabilitation, School of Sport Science, Shanghai University of Sport, Shanghai, 200438, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Zhongshan-Xuhui Affiliated Hospital of Fudan University, Shanghai 200031, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, Zhongshan-Xuhui Affiliated Hospital of Fudan University, Shanghai 200031, China.
authors.forename: Xingjun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Zhongshan-Xuhui Affiliated Hospital of Fudan University, Shanghai 200031, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Zhongshan-Xuhui Affiliated Hospital of Fudan University, Shanghai 200031, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, China. Electronic address: lujmhy6@sina.coml.
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu, 223300, China. Electronic address: aris_dr@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D019295:Computational Biology; D003251:Constriction, Pathologic / Q000235:genetics* / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009437:Neuralgia / Q000235:genetics* / Q000628:therapy; D020078:Neurogenic Inflammation / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000235:genetics* / Q000628:therapy; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D018836:Inflammation Mediators; D035683:MicroRNAs; C000620691:Mirn93 microRNA, rat; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat
keywords: Chronic constriction injury; Neuropathic pain; STAT3; miR-93