Differential Microarray Analysis of Human Placental microRNAs Revealed Upregulation of Angiogenesis-Associated microRNAs (miR-15a, miR-126, and miR-210) in Preeclampsia.

Abstract

Impaired placental angiogenesis is a hallmark of preeclampsia (PE) that affects ~7% of all human pregnancies. MicroRNAs are a class of noncoding 21-25 nucleotide RNAs that negatively regulate gene expression primarily at the level of post-transcription. MicroRNAs are differentially expressed in preeclamptic vs. normal placentas and angiogenesis associated ones are increased by PE. Placentas were collected from severe PE and healthy term pregnancies (n=10/group). Total microRNA samples were isolated from placental tissues by using the mirVanaTM miRNA isolation kit. Differential microRNA expression profiling of PE vs. normal placentas were performed with human microRNA array containing 894 mature microRNAs from miRBase database. Angiogenesis-associated microRNAs were analyzed by searching for their potential targets using online target prediction software (i.e., TargetScan, picTar, and RegRNA). Differentially expressed microRNAs of interest in PE placenta were confirmed by real-time quantitative RT-PCR. Differential microarray analysis identified 44 highly expressed placental microRNAs that differ significantly between PE and normal controls; 74 miRNAs were also differentially expressed but with low expression levels in human placenta. Bioinformatic analysis revealed that these microRNAs are involved in the expression of genes with various biological functions and a subset was associated with angiogenesis. With real-time PCR analysis we confirmed that three highly expressed placental microRNAs, i.e., miR-15a, miR-126 and miR-210, were upregulated in PE placentas. Placental microRNAs are differentially expressed in preeclamptic and healthy term human placentas. Upregulation of angiogenesis-associated microRNAs implicates a potential mechanism for deregulation of angiogenic genes by PE (NIH RO1 HL74947 & HL70562). (poster)