Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Genet Med. 2019 Mar;21(3):591-600. doi: 10.1038/s41436-018-0103-8. Epub 2018 Jul 12.
We studied microRNAs as potential biomarkers for Pompe disease.
We analyzed microRNA expression by small RNA-seq in tissues from the disease murine model at two different ages (3 and 9 months), and in plasma from Pompe patients.
In the mouse model we found 211 microRNAs that were differentially expressed in gastrocnemii and 66 in heart, with a different pattern of expression at different ages. In a preliminary analysis in plasma from six patients 55 microRNAs were differentially expressed. Sixteen of these microRNAs were common to those dysregulated in mouse tissues. These microRNAs are known to modulate the expression of genes involved in relevant pathways for Pompe disease pathophysiology (autophagy, muscle regeneration, muscle atrophy). One of these microRNAs, miR-133a, was selected for further quantitative real-time polymerase chain reaction analysis in plasma samples from 52 patients, obtained from seven Italian and Dutch biobanks. miR-133a levels were significantly higher in Pompe disease patients than in controls and correlated with phenotype severity, with higher levels in infantile compared with late-onset patients. In three infantile patients miR-133a decreased after start of enzyme replacement therapy and evidence of clinical improvement.
Circulating microRNAs may represent additional biomarkers of Pompe disease severity and of response to therapy.
我们研究了 microRNAs 作为庞贝病的潜在生物标志物。
我们通过小 RNA-seq 分析了疾病小鼠模型在两个不同年龄（3 个月和 9 个月）的组织以及庞贝病患者血浆中的 microRNA 表达。
在小鼠模型中，我们在腓肠肌中发现了 211 个差异表达的 microRNAs，在心脏中发现了 66 个，不同年龄的表达模式不同。在对六名患者血浆的初步分析中，有 55 个 microRNAs 差异表达。其中 16 个 microRNAs 与在小鼠组织中失调的 microRNAs 相同。这些 microRNAs 已知可调节与庞贝病病理生理学相关途径（自噬、肌肉再生、肌肉萎缩）的基因表达。其中一个 microRNA，miR-133a，被选择用于在从七个意大利和荷兰生物库获得的 52 名患者的血浆样本中进行进一步的定量实时聚合酶链反应分析。庞贝病患者的 miR-133a 水平明显高于对照组，与表型严重程度相关，婴儿型患者的水平高于晚发型患者。在三名婴儿型患者中，miR-133a 在开始酶替代治疗后降低，并出现临床改善的证据。
循环 microRNAs 可能是庞贝病严重程度和对治疗反应的额外生物标志物。
