Cushing Leah, Jiang Zhihua, Kuang Pingping, Lü Jining
Columbia Center for Human Development, Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, New York.
Am J Respir Cell Mol Biol. 2015 Apr;52(4):397-408. doi: 10.1165/rcmb.2014-0232RT.
Decades of studies have shown evolutionarily conserved molecular networks consisting of transcriptional factors, diffusing growth factors, and signaling pathways that regulate proper lung development. Recently, microRNAs (miRNAs), small, noncoding regulatory RNAs, have been integrated into these networks. Significant advances have been made in characterizing the developmental stage- or cell type-specific miRNAs during lung development by using approaches such as genome-wide profiling and in situ hybridization. Results from gain- or loss-of-function studies revealed pivotal roles of protein components of the miRNA pathway and individual miRNAs in regulating proliferation, apoptosis, differentiation, and morphogenesis during lung development. Aberrant expression or functions of these components have been associated with pulmonary disorders, suggesting their involvement in pathogenesis of these diseases. Moreover, genetically modified mice generated in these studies have become useful models of human lung diseases. Challenges in this field include characterization of collective function and responsible targets of miRNAs specifically expressed during lung development, and translation of these basic findings into clinically relevant information for better understanding of human diseases. The goal of this review is to discuss the recent progress on the understanding of how the miRNA pathway regulates lung development, how dysregulation of miRNA activities contributes to pathogenesis of related pulmonary diseases, and to identify relevant questions and future directions.
数十年的研究表明，存在由转录因子、扩散性生长因子和调节肺正常发育的信号通路组成的进化保守分子网络。最近，微小RNA（miRNA），即小的非编码调节RNA，已被纳入这些网络。通过全基因组分析和原位杂交等方法，在表征肺发育过程中特定发育阶段或细胞类型的miRNA方面取得了重大进展。功能获得或丧失研究的结果揭示了miRNA途径的蛋白质成分和单个miRNA在调节肺发育过程中的增殖、凋亡、分化和形态发生中的关键作用。这些成分的异常表达或功能与肺部疾病有关，表明它们参与了这些疾病的发病机制。此外，在这些研究中产生的基因工程小鼠已成为人类肺部疾病的有用模型。该领域的挑战包括表征肺发育过程中特异性表达的miRNA的集体功能和相关靶点，以及将这些基础研究结果转化为临床相关信息，以更好地理解人类疾病。本综述的目的是讨论在理解miRNA途径如何调节肺发育、miRNA活性失调如何导致相关肺部疾病的发病机制方面的最新进展，并确定相关问题和未来方向。
