Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2022 Sep 20;13:999211. doi: 10.3389/fendo.2022.999211. eCollection 2022.
Methamphetamine (METH) abuse can result in severe neurotoxicity, for which the mechanism is not yet clear. In the present study, we investigated the role of noncoding RNAs in METH-induced dopaminergic neurotoxicity, and analyzed the underlying mechanism using bioinformatic methods. We confirmed by flow cytometry that miR-129-1-3p is involved in promoting dopaminergic apoptosis under METH treatment and its role could be inhibited by a high concentration of circ_0015891. Also, we combined transcriptomic data with bioinformatics to explore the downstream mechanism of miR-129-1-3p regulation of METH-induced apoptosis, highlighted the potentially pivotal figure of response to nutrition. Further bioinformatic analysis of circ_0015891 was conducted as well and showed that circ_0015891 was the sponge of various microRNAs that effect apoptosis by different mechanisms. Collectively, we found a novel circ_0015891/miR-129-1-3p axis that may be a promising therapeutic target for METH-induced dopaminergic neurotoxicity.
甲基苯丙胺（METH）滥用可导致严重的神经毒性，其机制尚不清楚。在本研究中，我们使用生物信息学方法研究了非编码 RNA 在 METH 诱导的多巴胺能神经毒性中的作用，并分析了其潜在机制。我们通过流式细胞术证实，miR-129-1-3p 在 METH 处理下参与促进多巴胺能细胞凋亡，其作用可被 circ_0015891 的高浓度抑制。此外，我们结合转录组数据和生物信息学方法探讨了 miR-129-1-3p 调节 METH 诱导的细胞凋亡的下游机制，突出了对营养反应的潜在关键作用。我们还对 circ_0015891 进行了进一步的生物信息学分析，表明 circ_0015891 是各种 microRNA 的海绵，这些 microRNA 通过不同的机制影响细胞凋亡。综上所述，我们发现了一个新的 circ_0015891/miR-129-1-3p 轴，它可能是治疗 METH 诱导的多巴胺能神经毒性的有前途的治疗靶点。
