miRNAs regulate lung development and surfactant homeostasis via directly targeting SFTPC and TTF-1 in reprogramming-derived bovine model of NRDS

In this study, We proposed a reprogramming-derived bovine model of NRDS based on typical phenotypes of neonatal respiratory distress syndrome (NRDS) and high reproducibility and replication rates as well as a steerable background of neonatal cloned cows suffering from NRDS. With the aid of miRNA sequencing, construction of the miRNA–gene network and functional enrichment of target genes, the effects of specific miRNAs on lung development and surfactant homeostasis were determined in this model. We identified 12 miRNAs targeting SFTPB, SFTPC and NKX2-1 genes, demonstrated repression effects of three miRNAs on NKX2-1 and SFTPC expression in vivo and through which miRNAs disturbed lung development and surfactant homeostasis in the NRDS bovine model. Overall design: Two equal pools of total RNA (500 ng per sample), each from four cows, were produced from lung tissues of neonatal cloned and normal cows