Comprehensive analysis of the differential expression profile of microRNAs in missed abortion

Abstract

Abstract To screen the key circulating microRNAs (miRNAs) involved in missed abortion (MA) and explore their role in MA process. We examined the miRNA profile from the serum of three MA patients and three early pregnancy induced abortion patients (controls) by next‐generation sequencing. We analyzed the target genes of the differentially expressed (DE) miRNAs to analyze the function and pathway enrichment using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. We validated five candidate miRNAs by real time‐qPCR. Integrated miRNA‐mRNA‐pathway network analysis was performed to show the interaction network of the candidate miRNAs and their target genes of interest with the involved pathways. It was observed that 227 miRNAs were differently expressed between the MA group and the early pregnancy control group, with 58 miRNAs downregulated and 169 miRNAs upregulated in the MA group. Real‐time qPCR results revealed that expression of the five candidate miRNAs, namely hsa‐miR‐22‐3p, hsa‐miR‐145‐3p, hsa‐miR‐107, hsa‐miR‐361‐3p, and hsa‐miR‐378c, was consistent with the miRNA data obtained by sequencing. Integrated miRNA‐mRNA‐pathway network analysis illustrated that target genes of the candidate miRNAs were mainly involved in the PI3K‐Akt signaling pathway, HIF‐1 signaling pathway, and VEGF signaling pathway, which would have potential significance in pregnancy and MA. We are the first to reveal the DE miRNAs involved in MA and illustrate their functional interaction network. These results might provide potential circulating biomarkers and new therapeutic targets for MA.

Keywords

• miRNA profile
• miRNA‐mRNA‐pathway network
• missed abortion
• next‐generation sequencing