Attenuation of miR-17∼92 Cluster in Bronchopulmonary Dysplasia
Attenuation of miR-17∼92 Cluster in Bronchopulmonary Dysplasia
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DOI：
10.1513/annalsats.201501-058oc
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发表时间：
2015-10-01
影响因子：
8.3
通讯作者：
Tipple, Trent E.
中科院分区：
文献类型：
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作者：
Rogers, Lynette K.;Robbins, Mary;Tipple, Trent E.
理由：支气管肺发育不良仍然是新生儿发病的一个重要原因；然而，预测或预防支气管肺发育不良发展的新靶点的确定仍然难以实现。与 92 簇相似的适当的 microRNA (miR)-17 对于正常的肺部发育是必需的，并且在其他肺部疾病中也报道了表达的改变。我们工作的总体假设是，与 92 簇相似的 miR-17 表达改变有助于支气管肺发育不良的分子发病机制。 目的：当前的研究测试了支气管肺发育不良中存在与 92 簇相似的 miR-17 和 DNA 甲基转移酶表达的改变的假设。方法：与 92 簇表达相似的 miR-17、启动子 甲基化和 DNA 甲基转移酶表达是在死于支气管肺发育不良的早产儿或死于非呼吸原因的足月/近足月婴儿的尸检肺样本中测定的。与 92 个簇成员 miR-17 和 -19b 类似的 miR-17 表达在出生第一周从第二个机构的单独早产儿队列中收集的血浆样本中进行测量，这些早产儿随后被诊断为支气管肺发育不良。 测量和主要结果：尸检组织数据表明，与 92 类似的 miR-17 表达在支气管肺发育不良中显着较低 与没有支气管肺发育不良的对照受试者相比，其与启动子甲基化和 DNA 甲基转移酶表达呈负相关。血浆样本分析表明，在随后发生支气管肺发育不良的婴儿中，miR-17 和 -19b 表达降低。结论：我们的数据首次证明了 miR-17 的表达改变与支气管肺发育不良中的 92duster 类似。我们的尸检和血浆结果之间的一致性进一步支持我们的工作假设，即与 92 簇相似的 miR-17 有助于支气管肺发育不良的分子发病机制。
Rationale: Bronchopulmonary dysplasia remains a significant cause of neonatal morbidity; however, the identification of novel targets to predict or prevent the development of bronchopulmonary dysplasia remains elusive. Proper microRNA (miR)-17 similar to 92 cluster is necessary for normal lung development, and alterations in expression are reported in other pulmonary diseases. The overall hypothesis for our work is that altered miR-17 similar to 92 cluster expression contributes to the molecular pathogenesis of bronchopulmonary dysplasia.Objectives: The current studies tested the hypothesis that alterations in miR-17 similar to 92 cluster and DNA methyltransferase expression are present in bronchopulmonary dysplasia.Methods: miR-17 similar to 92 cluster expression, promoter methylation, and DNA methyltransferase expression were determined in autopsy lung samples obtained from premature infants who died with bronchopulmonary dysplasia, or from term/near-term infants who died from nonrespiratory causes. Expression of miR-17 similar to 92 cluster members miR-17 and -19b was measured in plasma samples collected in the first week of life from a separate cohort of preterm infants at a second institution in whom bronchopulmonary dysplasia was diagnosed subsequently.Measurements and Main Results: Autopsy tissue data indicated that miR-17 similar to 92 expression is significantly lower in bronchopulmonary dysplasia lungs and is inversely correlated with promoter methylation and DNA methyltransferase expression when compared with that of control subjects without bronchopulmonary dysplasia. Plasma sample analyses indicated that miR-17 and -19b expression was decreased in infants who subsequently developed bronchopulmonary dysplasia.Conclusions: Our data are the first to demonstrate altered expression of the miR-17 similar to 92 duster in bronchopulmonary dysplasia. The consistency between our autopsy and plasma findings further support our working hypothesis that the miR-17 similar to 92 cluster contributes to the molecular pathogenesis of bronchopulmonary dysplasia.