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Effects of XIST/miR‐137 axis on neuropathic pain by targeting TNFAIP1 in a rat model
Author(s) -
Zhao Ying,
Li Sen,
Xia Nin,
Shi Yan,
Zhao ChangMing
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26254
Subject(s) - xist , neuropathic pain , downregulation and upregulation , gene knockdown , biology , gene silencing , neurogenesis , pharmacology , microbiology and biotechnology , apoptosis , genetics , x inactivation , gene , x chromosome
Non‐coding RNAs have been reported to participate in the pathophysiology of neuropathic pain. The objective of our study was to investigate the biological role of XIST in neuropathic pain development. In our study, we identify and validate that lncRNA XIST was markedly increased and miR‐137 was significantly decreased in chronic constriction injury (CCI) rats. XIST silencing alleviated pain behaviors including both mechanical and thermal hyperalgesia in the CCI rats. XIST was predicted to interact with miR‐137 by bioinformatics technology and dual‐luciferase reporter assays confirmed the correlation between XIST and miR‐137. miR‐137 was negatively modulated by XIST and upregulation of miR‐137 greatly reduced neuropathic pain development in CCI rats. Moreover, we observed that tumor necrosis factor alpha‐induced protein 1 (TNFAIP1) was enhanced in CCI rats and 3′‐untranslated region (UTR) of TNFAIP1 was exhibited to be a target of miR‐137 by bioinformatics prediction. TNFAIP1 can act as a crucial inflammation regulator by activating NF‐kB activity. Overexpression of miR‐137 significantly suppressed TNFAIP1 both in vitro and in vivo. Furthermore, upregulation of XIST reversed the inhibitory role of miR‐137 in neuropathic pain development by inhibiting TNFAIP1. In conclusion, our current study indicates that XIST can positively regulate neuropathic pain in rats through regulating the expression of miR‐137 and TNFAIP1. Our results imply that XIST/miR‐137/TNFAIP1 axis may serve as a novel therapeutic target in neuropathic pain.