Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, College of Forensic Medicine, Hebei Medical University, Chinese Academy of Medical Sciences, Shijiazhuang 050017, China.
Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China.
Int J Mol Sci. 2024 Aug 16;25(16):8952. doi: 10.3390/ijms25168952.
A number of studies have reported that drug addiction is associated with microRNAs (miRNAs). However, the roles of plasma miRNAs in methamphetamine (METH) addicts have not been clearly explained. This study aimed to profile a panel of miRNAs as non-invasive predictive biomarkers and therapeutic targets for METH addiction. Differentially expressed miRNAs were derived from next-generation sequencing technology (NGS) and were validated by quantitative real-time PCR (RT-qPCR). The diagnostic value of specific altered miRNAs was evaluated by receiver operating characteristic (ROC) analysis and area under the curve (AUC). NGS results revealed that 63 miRNAs were significantly altered in the METH-exposed paradigm. The levels of hsa-miR-592, hsa-miR-9-3p, hsa-miR-206 and hsa-let-7b-3p were significantly elevated in the plasma of METH addicts. Hsa-miR-9-3p was a useful biomarker discriminating METH addicts from normal (AUC was 0.756). Importantly, combining detection of hsa-miR-592 and hsa-miR-9-3p achieved the highest AUC of 0.87, with a sensitivity and specificity of 82.7% and 78.9%, respectively. Target gene BDNF decreased significantly in METH addicts. Although METH addicts showed significant depressive symptoms, there was no correlation between the expression level of miR-592 and miR-9-3p and the degree of depression. Our findings suggested that hsa-miR-592, hsa-miR-9-3p, hsa-miR-206, and hsa-let-7b-3p may play a potential role in the pathology of METH addiction, and a combination of hsa-miR-592 and hsa-miR-9-3p could serve as potential peripheral biomarker and therapeutic target for METH addiction.
许多研究报道称,药物成瘾与 microRNAs(miRNAs)有关。然而,血浆 miRNAs 在甲基苯丙胺(METH)成瘾者中的作用尚未得到明确解释。本研究旨在分析一组 miRNA 作为非侵入性预测生物标志物和 METH 成瘾的治疗靶点。差异表达的 miRNA 源自下一代测序技术(NGS),并通过定量实时 PCR(RT-qPCR)进行验证。通过接收者操作特征(ROC)分析和曲线下面积(AUC)评估特定改变的 miRNA 的诊断价值。NGS 结果显示,63 个 miRNA 在 METH 暴露模型中显著改变。METH 成瘾者血浆中 hsa-miR-592、hsa-miR-9-3p、hsa-miR-206 和 hsa-let-7b-3p 的水平显著升高。hsa-miR-9-3p 是区分 METH 成瘾者和正常人的有用生物标志物(AUC 为 0.756)。重要的是,联合检测 hsa-miR-592 和 hsa-miR-9-3p 可实现最高 AUC 值为 0.87,灵敏度和特异性分别为 82.7%和 78.9%。BDNF 靶基因在 METH 成瘾者中显著减少。尽管 METH 成瘾者表现出明显的抑郁症状,但 miR-592 和 miR-9-3p 的表达水平与抑郁程度之间没有相关性。我们的研究结果表明,hsa-miR-592、hsa-miR-9-3p、hsa-miR-206 和 hsa-let-7b-3p 可能在 METH 成瘾的发病机制中发挥潜在作用,hsa-miR-592 和 hsa-miR-9-3p 的组合可能作为 METH 成瘾的潜在外周生物标志物和治疗靶点。