Department of Anesthesiology, Bao'an Maternity and Child Health Hospital, Shenzhen, China.
Department of Neurology, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
J Cell Physiol. 2018 Aug;233(8):6098-6106. doi: 10.1002/jcp.26453. Epub 2018 Mar 6.
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.
长非编码 RNA 被报道参与神经病理性疼痛的发展。X 染色体失活特异性转录本（XIST）参与多种癌症的进展。然而，XIST 在神经病理性疼痛中的作用尚不清楚。在本研究中，我们建立了慢性压迫损伤（CCI）大鼠模型，发现 XIST 在脊髓组织和分离的 CCI 大鼠小胶质细胞中均显著上调。抑制 XIST 抑制了机械性和热痛觉过敏等神经病理性疼痛行为。此外，XIST 的减少通过抑制 COX-2、肿瘤坏死因子（TNF）-α 和 IL-6 抑制了 CCI 大鼠中的神经炎症。先前，miR-150 已被报道通过靶向 TLR5 来抑制神经病理性疼痛。目前，miR-150 被预测为 XIST 的 miRNA 靶标，这表明 miR-150 和 XIST 之间呈负相关。miR-150 在 CCI 大鼠中显著减少，过表达 miR-150 可显著抑制神经炎症相关细胞因子。此外，ZEB1 被显示为 miR-150 的直接靶标，我们发现它在 CCI 大鼠中过表达。沉默 ZEB1 能够在体内抑制神经病理性疼痛，并且 XIST 的下调降低了 ZEB1，而 miR-150 抑制剂可以逆转这一情况。综上所述，我们表明，XIST 通过作为 miR-150 的海绵来上调 ZEB1 ，从而诱导 CCI 大鼠发生神经病理性疼痛。揭示了 XIST/miR-150/ZEB1 轴可作为神经病理性疼痛的治疗靶点。
