microRNA expression profiling and functional annotation analysis of their targets modulated by oxidative stress during embryonic heart development in diabetic mice

Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM. Bioinformatics analysis showed that the majority of the 2111 potential miRNA target genes were associated with cardiac development-related pathways including STAT3 and IGF-1 and transcription factors (Cited2, Zeb2, Mef2c, Smad4 and Ets1). Overexpression of the antioxidant enzyme, superoxide dismutase 1, reversed PGDM-altered miRNAs, suggesting that oxidative stress is responsible for dysregulation of miRNAs. Thus, our study provides the foundation for further investigation of a miRNA-dependent mechanism underlying PGDM-induced CHDs.