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XIST accelerates neuropathic pain progression through regulation of miR‐150 and ZEB1 in CCI rat models
Author(s) -
Yan XueTao,
Lu JingMin,
Wang Yu,
Cheng XiaoLi,
He XiangHu,
Zheng WenZhong,
Chen Hu,
Wang YanLin
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.26453
Subject(s) - xist , neuropathic pain , neuroinflammation , gene silencing , nociception , medicine , cancer research , pharmacology , inflammation , biology , x inactivation , receptor , biochemistry , x chromosome , gene
LncRNAs are reported to participate in neuropathic pain development. LncRNA X‐inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX‐2, tumor necrosis factor (TNF)‐α and IL‐6 and in CCI rats. Previously, miR‐150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR‐150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR‐150 and XIST. miR‐150 was remarkably decreased in CCI rats and overexpression of miR‐150 can significantly suppress neuroinflammation‐related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR‐150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR‐150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR‐150. It was revealed that XIST/miR‐150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.