Abnormal expression of microRNA-575 leads to missed abortion through regulating apoptosis and angiogenesis

Numerous microRNA (miR) are important for placental development and function. miR-575 has been demonstrated to be upregulated in maternal placenta in patients who have experienced a miscarriage. The present study aimed to explore the role of abnormal expression of miR-575 in missed abortion (MA) and to further analyze the potential molecular mechanisms. Embryo villus tissue samples were extracted from 10 childless women with MA and 10 fertile women without a history of MA. Additionally, human choriocarcinoma cells, JEG-3, were used in the present study, which were transfected with miR-575 mimic, inhibitor and scramble. The expression of miR-575 in embryo villus tissues and in JEG-3 cells was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Apoptosis in villus tissues of patients with MA and in JEG-3 cells of miR-575 mimic, inhibitor and scramble groups were detected by flow cytometry. Furthermore, the expression levels of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and phosphorylated (p)-p53, and angiogenesis-related proteins, including vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2), were measured by RT-qPCR and western blotting. Additionally, the target of miR-575 was predicted and clarified by luciferase reporter assay. miR-575 was significantly overexpressed in MA villus tissue compared with normal tissue (P<0.05). The percentage of apoptotic cells in MA embryo villus tissue was significantly higher than that in normal tissue (P<0.05). After JEG-3 cells were transfected with miR-575 inhibitor, the expression of miR-575 and the percentage of apoptotic cells decreased significantly compared with the control (P<0.05). MiR-575 suppression significantly increased the expression of Bcl-2 (P<0.05), and decreased the expressions of Bax (P<0.05) and p-p53 (P<0.01) compared with the control. Furthermore, miR-575 suppression significantly increased the expressions of angiogenesis-related proteins, Ang-2 and VEGF (P<0.01). Superoxide dismutase 2 was identified as the target of miR-575. Therefore, abnormal expression of miR-575 may lead to MA through regulating apoptosis and angiogenesis. Inhibition of miR-575 may inhibit apoptosis and promote angiogenesis in MA.