microRNA-21 regulates the proliferation of placental cells via FOXM1 in preeclampsia.

The present study determined the expression of microRNA (miRNA or miR)-21 and forkhead box M1 (FOXM1) in placenta and blood samples from patients with preeclampsia (PE), and investigated the relationship between miR-21 and FOXM1. A total of 32 pregnant women with PE and 28 healthy pregnant women were included in the study as the experimental and control groups, respectively. Placental tissues and peripheral blood were collected from all subjects. ELISA was performed to measure the level of FOXM1 protein in the blood. HTR8/SVneo cells overexpressing miR-21 were established by transfection with agomiR-21. Reverse transcription-quantitative PCR was performed to measure the expression of FOXM1 mRNA and miR-21 in the placenta, blood and cells, and western blotting was used to evaluate FOXM1 protein expression in the placenta. An MTT assay was also performed to assess cell viability. In addition, a dual-luciferase reporter assay was used to investigate the direct interaction between FOXM1 and miR-21. The occurrence of PE was found to be associated with reduced FOXM1 mRNA levels, and elevated FOXM1 protein expression may serve a regulatory role that when attenuated leads to the occurrence of PE. Furthermore, miR-21 may serve a regulatory role in the pathology of PE by downregulating FOXM1 expression at the transcriptional level. In HTR8/SVneo cells, the overexpression of miR-21 reduced cell viability, possibly via the reduction of FOXM1 expression. The dual-luciferase assay indicated that miR-21 directly binds to the 3'-untranslated region of FOXM1 to regulate its expression. The present study demonstrated that the expression of FOXM1 mRNA and protein is downregulated, whereas the expression of miR-21 is upregulated in the placenta and blood samples of PE patients. In conclusion, miR-21 may regulate placental cell proliferation via its effects on FOXM1 to promote the occurrence and development of PE.