MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level

Obstetric antiphospholipid syndrome is initiated by the action of antiphospholipid antibodies on placenta. The characteristics of APS in pregnancy include vascular thrombosis, inflammation and impairment of trophoblast implantation. MicroRNA (miRNA) expression has been suggested as one of the genetic factors that contribute to the development of this syndrome. miRNAs regulate gene expressions in a vast assortment of cellular biological mechanisms include the development of placental tissue. Hence, further investigation on the regulation of placental miRNA in APS is required. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesized signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation from the qPCR data while retinoblastoma gene (RET), dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.