Table7_Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome.XLSX

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research.Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.

引言：胎内暴露于阿片类药物的新生儿，产后常出现一组称为新生儿阿片类药物戒断综合征（NOWS）的戒断症状。近年来，由于阿片类药物流行病的加剧，NOWS的发病率有所上升。microRNAs（miRNAs）是一类小型非编码RNA分子，在基因调控中发挥着至关重要的作用。miRNAs的表观遗传变异及其对成瘾相关过程的影响是一个快速发展的研究领域。方法：本研究采用Illumina Infinium Methylation EPIC BeadChip分析96个人胎盘组织中miRNA编码基因的DNA甲基化水平，以鉴定与NOWS相关的miRNA基因甲基化谱：其中32例来自需要药物治疗NOWS的孕妇，32例来自无需治疗的孕妇，以及32例未暴露于阿片类药物的健康对照者。结果：研究共鉴定出46个与47个独特miRNA相关的显著差异甲基化（FDR p-value ≤ 0.05）的CpG位点，其中包含28个低甲基化和18个高甲基化的CpG位点，其受试者工作特征（ROC）曲线下面积（AUC）≥0.75，这些异常的miRNA甲基化模式可能成为NOWS发病机制的一个影响因素。结论：这是首项分析NOWS婴儿miRNA甲基化谱的研究，展示了miRNAs在诊断和治疗该疾病中可能具有的独特作用。此外，这些数据可能为NOWS婴儿的精准医疗提供了一种可行的途径。