Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
PLoS One. 2011 Feb 28;6(2):e14736. doi: 10.1371/journal.pone.0014736.
As playing important roles in gene regulation, microRNAs (miRNAs) are believed as indispensable involvers in the pathogenesis of myocardial infarction (MI) that causes significant morbidity and mortality. Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt.
A long-term MI model of rat was established in this study. The microarray technology was applied to determine the global miRNA expression change intervened by propranolol. Multiple network analyses were sequentially applied to evaluate the regulatory capacity, efficiency and emphasis of the miRNAs which dysexpression in MI were significantly reversed by propranolol.
Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart. Our network analysis identified that, among these miRNAs, the prime players in MI were miR-1, miR-29b and miR-98. Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively.
Our study illustrates how a combination of microarray technology and functional protein network analysis can be used to identify disease-related key miRNAs.
作为基因调控中发挥重要作用的 microRNAs（miRNAs），被认为是心肌梗死（MI）发病机制中不可或缺的参与者，导致了相当高的发病率和死亡率。基于这样一种假设，即仅对 miRNA 超家族中的某些关键成员进行调节就可能有益于缺血性心脏，我们提出了一种基于微阵列的网络生物学方法，并用普萘洛尔公认的临床疗效作为提示来识别它们。
本研究建立了大鼠长期 MI 模型。应用微阵列技术来确定普萘洛尔干预下的全球 miRNA 表达变化。然后依次应用多种网络分析来评估 miRNA 的调控能力、效率和重点，这些 miRNA 在 MI 中的表达失调被普萘洛尔显著逆转。
微阵列数据分析表明，长期普萘洛尔给药导致 MI 中 18 个失调 miRNA 中的 18 个表达发生逆转，这意味着有意调节 miRNA 表达可能对缺血性心脏有有利影响。我们的网络分析确定，在这些 miRNA 中，miR-1、miR-29b 和 miR-98 是 MI 中的主要调控者。进一步的研究发现，miR-1 主要集中在调节心肌细胞生长，而 miR-29b 和 miR-98 则分别强调纤维化和炎症。
我们的研究说明了如何结合微阵列技术和功能蛋白质网络分析来识别与疾病相关的关键 miRNA。
