Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, 314001, China.
Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, 314001, China.
Biochem Biophys Res Commun. 2023 Nov 19;682:97-103. doi: 10.1016/j.bbrc.2023.09.069. Epub 2023 Sep 29.
Due to its complex pathological mechanisms, bone cancer pain (BCP) has become an increasingly challenging clinical issue, there is an urgent need to identify the underlying mechanisms of BCP. In our present study, we found that decreased expression of miR-199a-3p in spinal dorsal horn (SDH) neurons contributed to BCP hypersensitivity. Intrathecal administration of miR-199a-3p agomir alleviated the initiation of tumor inoculation induced pain hypersensitivity and suppressed the expression of DNMT3A. Subsequently, luciferase assays confirmed direct binding between miR-199a-3p and Dnmt3a mRNA. AAV-DNMT3A-shRNA microinjection relieved mechanical hyperalgesia and upregulated the expression of Nrf2 levels in BCP. In naïve rats, Overexpression of DNMT3A yielded the opposite effects. Finally, increase of DNMT3A by lentiviral vector abolished miR-199a-3p-mediated alleviation hypersensitivity effects on BCP progression. Taken these together, our findings highlighted a novel contribution of miR-199a-3p to BCP and provided a fresh outlook on potential mechanism research for BCP.
由于其复杂的病理机制，骨癌痛（BCP）已成为一个日益具有挑战性的临床问题，因此迫切需要确定 BCP 的潜在机制。在本研究中，我们发现脊髓背角（SDH）神经元中 miR-199a-3p 的表达下调导致 BCP 敏感性增加。鞘内给予 miR-199a-3p 激动剂可减轻肿瘤接种引起的痛觉过敏的发生，并抑制 DNMT3A 的表达。随后，荧光素酶报告基因实验证实 miR-199a-3p 与 Dnmt3a mRNA 之间存在直接结合。AAV-DNMT3A-shRNA 微注射可缓解机械性痛觉过敏，并上调 BCP 中 Nrf2 水平的表达。在未处理的大鼠中，过表达 DNMT3A 则产生相反的效果。最后，慢病毒载体增加 DNMT3A 可消除 miR-199a-3p 对 BCP 进展缓解敏感性的作用。综上所述，这些结果强调了 miR-199a-3p 在 BCP 中的新作用，并为 BCP 的潜在机制研究提供了新的视角。
