MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers

Abstract

Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes.

Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

“…We found significantly increased levels of 47 miRNAs in longissimus dorsi muscle (LDM) from IUGR fetuses compared to AGA fetuses at 63 dpc ( Figure 2 ). In recent studies, we investigated the role of miRNAs in pathophysiology of pregnancy-associated disorders and identified potential biomarker miRNAs for pregnancy complications [ 55 , 56 , 57 ]. Out of 47 upregulated miRNAs reported in this study, dysregulation of five miRNAs including miR-34a, miR-210, miR-199a, miR-363, and miR-16 in placenta or maternal circulation has been previously linked with pathophysiology of IUGR [ 57 , 58 ].…”

“…In recent studies, we investigated the role of miRNAs in pathophysiology of pregnancy-associated disorders and identified potential biomarker miRNAs for pregnancy complications [ 55 , 56 , 57 ]. Out of 47 upregulated miRNAs reported in this study, dysregulation of five miRNAs including miR-34a, miR-210, miR-199a, miR-363, and miR-16 in placenta or maternal circulation has been previously linked with pathophysiology of IUGR [ 57 , 58 ]. According to our results, from downregulated genes in LDM from IUGR fetuses, miR-34a, miR-210, miR-199a, miR-363, and miR-16 can potentially target 232, 220, 99, 29, and 29 genes, respectively ( Table S2 ).…”

“…We found significantly increased levels of 47 miRNAs in longissimus dorsi muscle (LDM) from IUGR fetuses compared to AGA fetuses at 63 dpc (Figure 2). In recent studies, we investigated the role of miRNAs in pathophysiology of pregnancy-associated disorders and identified potential biomarker miRNAs for pregnancy complications [55][56][57]. Out of…”

Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection

“…In methodology, a KTR-specific miR-PPIN was constructed and topological characterization was conducted to uncover theoretical hypothesis for miRNA biomarker discovery. Compared with traditional methods that equally rank the contribution of miRNAs in miRNA-mRNA network [ 42 , 43 ], the network system in this study was expanded by reasonably weighting the interaction among targets of miRNAs based on downstream PPI analysis. Hence in this model, the topological importance of genes targeted by miRNAs was prioritized according to their structural characteristics in PPIN.…”

Preeclampsia and Cardiovascular Risk for Offspring

“…Since human nephrogenesis occurs in the third trimester of pregnancy, when PE is often the most staggering, it is reasonable that the resulting changes in blood flow and circulatory factors may adversely affect the fetal kidneys. PE is known to be the major cause of IUGR and preterm labor [ 70 , 71 ]. IUGR, due to uteroplacental insufficiency, results in a nephron deficiency and glomerular hypertrophy in both male and female rats [ 72 ].…”