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：在子宫内暴露于阿片类药物的胎儿，在出生后常会面临一系列的戒断症状，这一症状群通常被称为新生儿阿片类药物戒断综合征（NOWS）。近年来，由于阿片类药物的流行，NOWS的发病率有所上升。微RNA（miRNA）是一类小型的非编码RNA分子，在基因调控中发挥着至关重要的作用。微RNA（miRNA）的表观遗传变异及其对成瘾相关过程的影响，是研究领域的快速发展的前沿。方法：本研究利用Illumina Infinium Methylation EPIC BeadChip分析了96例人胎盘组织中miRNA编码基因的DNA甲基化水平，以识别与NOWS相关的miRNA基因甲基化谱：其中32例来自需要药物治疗以管理NOWS的孕产妇，32例来自无需治疗NOWS的孕产妇，以及32例未暴露于阿片类药物的对照组。结果：研究识别出46个与47种独特miRNA相关的显著差异甲基化（FDR p值≤0.05）的CpG位点，其中ROC曲线下面积（AUC）≥0.75的包括28个低甲基化和18个高甲基化的CpG位点，这些可能被与NOWS相关联的失调微RNA甲基化模式可能是NOWS发病机制的一个促成因素。结论：这是首项分析NOWS婴儿miRNA甲基化谱的研究，展示了miRNA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婴儿的精准医学治疗提供了一个可能的方向。