Abu-Halima Masood, Meese Eckart, Keller Andreas, Abdul-Khaliq Hashim, Rädle-Hurst Tanja
Department of Human Genetics, Saarland University, 66421, Homburg/Saar, Germany.
Department of Human Genetics, Saarland University Medical Center, Kirrberger Straße 100, 66421, Homburg/Saar, Germany.
J Transl Med. 2017 Jul 10;15(1):156. doi: 10.1186/s12967-017-1255-z.
MicroRNAs (miRNAs) are a class of regulatory RNAs that regulate gene expression post-transcriptionally. Little, however, is known on the expression profile of circulating miRNAs in Tetralogy of Fallot (TOF) patients late after surgical repair. In this study, we aimed to identify the specific patterns of circulating miRNAs in blood of patients with repaired, non-syndromic TOF and to assess whether these specific miRNAs may be useful to differentiate patients with and without heart failure.
SurePrint™ 8 × 60 K Human v16 miRNA arrays were used to determine miRNA expression profiles in 15 healthy controls and 37 patients after TOF repair of whom 3 had symptomatic right heart failure. The expression levels of selected miRNAs have been validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools.
Compared with healthy controls, a total of 49, 58 and 77 miRNAs were found to be significantly altered in TOF patients (TOF-all), TOF patients with (TOF-HF) and without symptomatic right heart failure (TOF-noHF) (>2.0-fold change, adjusted P < 0.05), respectively. Three miRNAs namely miR-181d-5p, miR-206 and miR-625-5p were validated by RT-qPCR in all TOF groups. The area under the receiver operating characteristic curve (AUC) for miR-181d-5p, miR-206 and miR-625-5p were 0.987, 0.993 and 0.769 in TOF-all and 0.990, 0.994 and 0.749 in TOF-noHF, respectively. Moreover, expression levels of miR-625-5p, miR-1233-3p and miR-421 were lower in TOF-HF compared to TOF-noHF (P = 0.012).
Altered expression levels of circulating miRNAs were found in TOF patients late after surgical repair and are different to those seen in the right ventricular myocardium of infants with TOF. Expression levels of miR-421, miR-1233-3p and miR-625-5p are lower in TOF patients with symptomatic right heart failure and thus may indicate disease progression in these patients.
微小RNA（miRNA）是一类在转录后调节基因表达的调控RNA。然而，对于法洛四联症（TOF）患者术后晚期循环miRNA的表达谱了解甚少。在本研究中，我们旨在确定经手术修复的非综合征性TOF患者血液中循环miRNA的特定模式，并评估这些特定的miRNA是否有助于区分有无心力衰竭的患者。
使用SurePrint™ 8×60K人类v16 miRNA芯片来确定15名健康对照者和37名TOF修复术后患者的miRNA表达谱，其中3例有症状性右心衰竭。所选miRNA的表达水平已通过定量逆转录聚合酶链反应（RT-qPCR）进行验证。使用生物信息学工具预测miRNA表达改变的富集分析。
与健康对照者相比，分别在TOF患者（TOF-全体）、有症状性右心衰竭的TOF患者（TOF-HF）和无有症状性右心衰竭的TOF患者（TOF-无HF）中发现共有49、58和77种miRNA有显著改变（变化倍数>2.0，校正P<0.05）。在所有TOF组中，通过RT-qPCR验证了三种miRNA，即miR-181d-5p、miR-206和miR-625-5p。在TOF-全体中，miR-181d-5p、miR-206和miR-625-5p的受试者工作特征曲线下面积（AUC）分别为0.987、0.993和0.769；在TOF-无HF中分别为0.990、0.994和0.749。此外，与TOF-无HF相比，TOF-HF中miR-625-5p、miR-1233-3p和miR-421的表达水平较低（P=0.012）。
在TOF患者术后晚期发现循环miRNA的表达水平发生改变，且与TOF婴儿右心室心肌中的情况不同。有症状性右心衰竭的TOF患者中miR-421、miR-1233-3p和miR-625-5p的表达水平较低，因此可能表明这些患者的疾病进展。
