The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Neurology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
J Cell Physiol. 2020 Oct;235(10):6528-6535. doi: 10.1002/jcp.29465. Epub 2020 Feb 3.
The dysfunction of the nervous system contributes to neuropathic pain. Long noncoding RNAs are reported to participate in neuropathic pain. Recently, Linc00052 is implicated to be closely associated with multiple diseases. Nevertheless, the mechanisms of Linc00052 remain barely explored in neuropathic pain development. Currently, spinal nerve ligation (SNL) triggered neuropathic pain was employed in our investigation. Here, we assessed the function of Linc00052 in SNL rat models. Interestingly, we reported Linc00052 was significantly elevated in SNL rats. Loss of Linc00052 could reduce neuropathic pain progression via regulating the behaviors of neuropathic pain. Additionally, knockdown of Linc00052 repressed the processes of neuroinflammation. Interleukin (IL)-6 and tumor necrosis factor α level were inhibited while IL-10 was induced by the silence of Linc00052. Moreover, we predicted miR-448 can serve as a target of Linc00052. miR-448 exerts a crucial power in several diseases. Currently, we exhibited miR-448 was remarkably downregulated in SNL rats. RNA immunoprecipitation experiments validated the association between miR-448 and Linc00052. Inhibition of Linc00052 could reverse the roles of miR-448 on neuropathic pain development. Furthermore, Janus kinase 1 (JAK1) was displayed as the putative target of miR-448 in the present investigation. It was showed that JAK1 was induced in SNL rats. Loss of miR-448 could dramatically induce the expression of JAK1, which was rescued by knockdown of Linc00052. Taken these together, our study implied that Linc00052 functioned as a novel target of neuropathic pain via sponging miR-448 and regulating JAK1.
神经系统功能障碍导致神经性疼痛。长链非编码 RNA 被报道参与神经性疼痛。最近，Linc00052 被认为与多种疾病密切相关。然而，Linc00052 在神经性疼痛发展中的机制仍未得到充分探索。目前，我们在研究中采用了脊神经结扎（SNL）引发的神经性疼痛模型。在这里，我们评估了 Linc00052 在 SNL 大鼠模型中的功能。有趣的是，我们报道 Linc00052 在 SNL 大鼠中显著升高。通过调节神经性疼痛的行为，缺失 Linc00052 可以减少神经性疼痛的进展。此外，敲低 Linc00052 抑制了神经炎症的过程。沉默 Linc00052 抑制了白细胞介素（IL）-6 和肿瘤坏死因子 α 的水平，同时诱导了 IL-10 的产生。此外，我们预测 miR-448 可以作为 Linc00052 的靶点。miR-448 在几种疾病中发挥着重要作用。目前，我们发现 miR-448 在 SNL 大鼠中显著下调。RNA 免疫沉淀实验验证了 miR-448 与 Linc00052 之间的关联。抑制 Linc00052 可以逆转 miR-448 对神经性疼痛发展的作用。此外，在本研究中，Janus 激酶 1（JAK1）被显示为 miR-448 的潜在靶点。结果表明，JAK1 在 SNL 大鼠中被诱导。缺失 miR-448 可以显著诱导 JAK1 的表达，而敲低 Linc00052 可以挽救这一作用。综上所述，我们的研究表明，Linc00052 通过海绵吸附 miR-448 并调节 JAK1，作为神经性疼痛的一个新靶点发挥作用。
