Table10_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：宫内暴露于阿片类物质的新生儿在产后会出现一系列戒断症状，通常被称为新生儿阿片类戒断综合征（Neonatal Opioid Withdrawal Syndrome, NOWS）。近年来受阿片类物质流行的影响，NOWS的发病率呈上升趋势。微小RNA（MicroRNAs, miRNAs）是一类小型非编码RNA分子，在基因调控中发挥关键作用。微小RNA的表观遗传变异及其与成瘾相关过程的关联，是当前研究快速发展的领域之一。
方法：本研究采用Illumina Infinium甲基化EPIC芯片（Illumina Infinium Methylation EPIC BeadChip），对96份人胎盘组织中编码微小RNA的基因的DNA甲基化水平进行分析，以筛选与NOWS相关的微小RNA基因甲基化谱。其中32份样本来自产前暴露于阿片类物质且其所生新生儿需接受药物治疗的NOWS患儿母亲，32份来自产前暴露于阿片类物质但其所生新生儿无需接受NOWS治疗的母亲，剩余32份为未暴露对照组样本。
结果：本研究共筛选出46个与47个独特微小RNA相关的差异显著甲基化CpG位点（错误发现率（False Discovery Rate, FDR）p值≤0.05），其受试者工作特征曲线（Receiver Operating Characteristic, ROC）下面积（Area Under the Curve, AUC）≥0.75，其中包括28个低甲基化位点与18个高甲基化位点，这些位点均可能与NOWS相关。这些失调的微小RNA甲基化模式可能是NOWS发病机制的潜在影响因素。
结论：本研究是首个针对NOWS患儿的微小RNA甲基化谱进行分析的研究，阐明了微小RNA在该疾病诊断与治疗中可能发挥的独特作用。此外，本研究数据还可为实现NOWS患儿的可行精准医学方案提供前期基础。