Department of Anesthesiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Department of Anesthesiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Gene. 2020 Nov 30;761:145038. doi: 10.1016/j.gene.2020.145038. Epub 2020 Aug 8.
Neuropathic pain, which results from impairment of the somatosensory system, has affected about 8% population around the world and leads to considerable burdens for patients and world health care system. However, its underlying mechanisms remain poorly understood. In this study, we hypothesized that miR-24-3p was involved in the progression of neuropathic pain in CCI rat models. By measuring miR-24-3p expression in CCI rats, we found that miR-24-3p expression was increased in CCI rats, suggesting miR-24-3p might participate in neuropathic pain progression. Next, by conducting a serial in vitro and vivo experiments, we found that miR-24-3p regulated Wnt5a/β-Catenin Signaling levels to promote neuropathic pain progression via targeting LPAR3 in CCI rats. Furthermore, we explored the upstream regulator of miR-24-3p by conducting bioinformatics analysis, we found that circular RNA cZRANB1 might sponge to miR-24-3p. Then we applied biotinylated RNA pull-down and luciferase reporter assays to assess the association between cZRANB1 and miR-24-3p. It was found that cZRANB1 mediated LPAR3 expression via sponging miR-24-3p. Collectively, our study suggests that cZRNAB1 regulated Wnt5a/β-Catenin Signaling expression via miR-24-3p/LPAR3 axis in CCI rat models.
神经性疼痛是由躯体感觉系统损伤引起的，全球约有 8%的人口受到影响，给患者和世界卫生保健系统带来了相当大的负担。然而，其潜在机制仍知之甚少。在这项研究中，我们假设 miR-24-3p 参与了CCI 大鼠模型中神经性疼痛的进展。通过测量 CCI 大鼠中 miR-24-3p 的表达，我们发现 miR-24-3p 在 CCI 大鼠中表达增加，表明 miR-24-3p 可能参与神经性疼痛的进展。接下来，通过一系列的体外和体内实验，我们发现 miR-24-3p 通过靶向 CCI 大鼠中的 LPAR3 来调节 Wnt5a/β-连环蛋白信号水平，从而促进神经性疼痛的进展。此外，我们通过生物信息学分析探索了 miR-24-3p 的上游调节剂，发现环状 RNA cZRANB1 可能与 miR-24-3p 结合。然后我们应用生物素化 RNA 下拉和荧光素酶报告基因检测来评估 cZRANB1 和 miR-24-3p 之间的关联。结果发现，cZRANB1 通过海绵 miR-24-3p 来介导 LPAR3 的表达。总之，我们的研究表明，cZRNAB1 通过 miR-24-3p/LPAR3 轴调节 CCI 大鼠模型中的 Wnt5a/β-连环蛋白信号表达。
