Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.
Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg/Saar, Germany.
Cells. 2021 Apr 30;10(5):1066. doi: 10.3390/cells10051066.
Little is known about abundance level changes of circulating microRNAs (miRNAs) and messenger RNAs (mRNA) in patients with Ebstein's anomaly (EA). Here, we performed an integrated analysis to identify the differentially abundant miRNAs and mRNA targets and to identify the potential therapeutic targets that might be involved in the mechanisms underlying EA. A large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 EA patients and 16 age and gender-matched healthy control volunteers (HVs). Differential abundance level of single miRNA and mRNA was validated by Real-Time quantitative PCR (RT-qPCR). Enrichment analyses of altered miRNA and mRNA abundance levels were identified using bioinformatics tools. Altered miRNA and mRNA abundance levels were observed between EA patients and HVs. Among the deregulated miRNAs and mRNAs, 76 miRNAs (49 lower abundance and 27 higher abundance, fold-change of ≥2) and 29 mRNAs (25 higher abundance and 4 lower abundance, fold-change of ≥1.5) were identified in EA patients compared to HVs. Bioinformatics analysis identified 37 pairs of putative miRNA-mRNA interactions. The majority of the correlations were detected between the lower abundance level of miRNA and higher abundance level of mRNA, except for let-7b-5p, which showed a higher abundance level and their target gene, showed a lower abundance level. Pathway enrichment analysis of the deregulated mRNAs identified 35 significant pathways that are mostly involved in signal transduction and cellular interaction pathways. Our findings provide new insights into a potential molecular biomarker(s) for the EA that may guide the development of novel targeting therapies.
关于埃布斯坦畸形（EA）患者循环 microRNAs（miRNAs）和信使 RNAs（mRNA）丰度水平的变化知之甚少。在这里，我们进行了综合分析，以确定差异丰度的 miRNA 和 mRNA 靶标，并确定可能参与 EA 潜在机制的潜在治疗靶点。对 16 名 EA 患者和 16 名年龄和性别匹配的健康对照志愿者（HV）的血液进行了大量人类 miRNA 和 mRNA 微阵列分析，以确定全基因组表达谱。通过实时定量 PCR（RT-qPCR）验证单个 miRNA 和 mRNA 的差异丰度水平。使用生物信息学工具鉴定改变的 miRNA 和 mRNA 丰度水平的富集分析。在 EA 患者和 HV 之间观察到改变的 miRNA 和 mRNA 丰度水平。在失调的 miRNA 和 mRNA 中，与 HV 相比，76 个 miRNA（49 个下调和 27 个上调，倍数变化≥2）和 29 个 mRNA（25 个上调和 4 个下调，倍数变化≥1.5）在 EA 患者中被鉴定出。生物信息学分析确定了 37 对假定的 miRNA-mRNA 相互作用。除了 let-7b-5p 外，大多数相关性都在 miRNA 下调水平和 mRNA 上调水平之间检测到，而 let-7b-5p 则表现出较高的上调水平，其靶基因则表现出较低的下调水平。失调 mRNA 的途径富集分析确定了 35 个显著途径，这些途径主要涉及信号转导和细胞相互作用途径。我们的研究结果为 EA 的潜在分子生物标志物提供了新的见解，可能为新型靶向治疗的发展提供指导。
