Department of Orthopedics, The Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University, Huai'an Jiangsu, China.
Department of Anesthesiology, The Affiliated Huai'an NO.1 People's Hospital of Nanjing Medical University, Huai'an Jiangsu, China.
Biochem Biophys Res Commun. 2019 Sep 24;517(3):532-537. doi: 10.1016/j.bbrc.2019.07.061. Epub 2019 Jul 31.
MicroRNAs (miRNA) are reported to be a vital regulator of neuropathic pain. Even so, the molecular mechanisms of miRNA function on neuropathic pain development are known little. Our research was designed to investigate the role of miRNA in neuropathic pain development in rat modle set up by chronic sciatic nerve injury (CCI). Increasing miR-150 expression could significantly alleviate neuropathic pain in CCI rats. For farther researching the regulation mechanism of miR-150 on neuropathic pain, we screened AKT3 as a possible target of miR-150 by bioinformatic mechods and predicted a possible target of miR-150 in 3'-untranslated region (UTR) of AKT3 who serves as an oncogene. In rat model, the expression both of AKT3 mRNA and protein were significantly upregulated. The overexpressed miR-150 importantly repressed the level of AKT3 and simultaneously alleviate mechanical and thermal hyperalgesia in rat model. These suppressant impacts of miR-150 on neuropathic pain process can be reversed by the overexpression of AKT3. Considering all above results, our research declared that miR-150 can restrain neuropathic pain process though targeting AKT3 in vivo, suggesting that miR-150 could be the therapeutic target for neuropathic pain therapy by regulating AKT3.
微小 RNA（miRNA）被报道是神经性疼痛的重要调节因子。即便如此，miRNA 对神经性疼痛发展的作用的分子机制仍知之甚少。我们的研究旨在通过慢性坐骨神经损伤（CCI）大鼠模型来研究 miRNA 在神经性疼痛发展中的作用。增加 miR-150 的表达可显著缓解 CCI 大鼠的神经性疼痛。为了进一步研究 miR-150 对神经性疼痛的调节机制，我们通过生物信息学方法筛选 AKT3 作为 miR-150 的可能靶标，并预测 AKT3 的 3'-非翻译区（UTR）可能是一个作为致癌基因的 miR-150 的靶标。在大鼠模型中，AKT3 mRNA 和蛋白的表达均显著上调。过表达的 miR-150 显著抑制 AKT3 的水平，同时缓解大鼠模型中的机械和热痛觉过敏。miR-150 对神经性疼痛过程的这种抑制作用可以通过 AKT3 的过表达而逆转。考虑到所有上述结果，我们的研究表明，miR-150 可以通过靶向 AKT3 来抑制体内神经性疼痛过程，提示 miR-150 可以通过调节 AKT3 成为神经性疼痛治疗的治疗靶点。
