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Published on: March 30, 2019
Comprehensive analysis of the differential expression profile of microRNAs in missed abortion
Qiao-Xian Tian1,2, Shu-Hua Xia2, Ya-Hua Wu2
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
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.
Insights
This study identifies key circulating microRNAs (miRNAs) involved in missed abortion (MA). These findings may offer novel biomarkers and therapeutic targets for MA, improving pregnancy outcomes.
Area of Science:
- Reproductive biology
- Molecular genetics
- Biomarker discovery
Background:
- Missed abortion (MA) is a pregnancy complication with complex underlying mechanisms.
- Identifying circulating microRNAs (miRNAs) associated with MA is crucial for understanding its pathogenesis and developing diagnostic tools.
Purpose of the Study:
- To screen key circulating microRNAs (miRNAs) implicated in missed abortion (MA).
- To explore the functional roles and interaction networks of these differentially expressed miRNAs in the MA process.
- To identify potential circulating biomarkers and therapeutic targets for MA.
Main Methods:
- Serum miRNA profiling using next-generation sequencing in MA patients and controls.
- Bioinformatic analysis of differentially expressed miRNAs, including target gene prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.
- Validation of candidate miRNAs using real-time quantitative polymerase chain reaction (RT-qPCR).
- Integrated miRNA-mRNA-pathway network analysis.
Main Results:
- A total of 227 differentially expressed miRNAs were identified between MA and control groups (169 upregulated, 58 downregulated).
- Five candidate miRNAs (hsa-miR-22-3p, hsa-miR-145-3p, hsa-miR-107, hsa-miR-361-3p, and hsa-miR-378c) were validated by RT-qPCR.
- Target genes of these miRNAs are significantly enriched in pathways crucial for pregnancy, including PI3K-Akt, HIF-1, and VEGF signaling.
Conclusions:
- This study reveals differentially expressed miRNAs and their functional interaction network in missed abortion.
- The identified miRNAs and pathways hold potential as circulating biomarkers for MA diagnosis.
- These findings suggest novel therapeutic targets for managing missed abortion and improving reproductive health.
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