Up-regulation of miR-517-5p inhibits ERK/MMP-2 pathway: potential role in preeclampsia

Objective: To investigate the potential role of miRNA-517-5p in preeclampsia and its underlying mechanism.

Materials and methods: Placenta samples were obtained from 20 women with preeclampsia and 20 women with normal pregnancies. Expression level of miR-517-5p in placenta samples and JAR cells was detected. MiRNA-517-5p mimics or inhibitor was transfected in JAR cells, followed by detection of proliferative and invasive abilities of JAR cells. In addition, the expressions of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK) and matrix metalloproteinase-2 (MMP-2) in JAR cells were evaluated by Western blot. Meanwhile, the mRNA level of MMP-2 was evaluated by Real-time polymerase chain reaction (PCR). The luciferase assay was applied to identify the target gene of miRNA-517-5p.

Results: Increased level of miR-517-5p was detected in placenta samples of preeclampsia patients compared with normal pregnancies. MiRNA-517-5p could regulate proliferative and invasive abilities of JAR cells. Furthermore, miRNA-517-5p could regulate ERK/MMP-2 pathway in JAR cells, which would contribute to the pathophysiology of preeclampsia. The luciferase assay showed MMP-2 was the target gene of miR-517-5p. Further studies showed that MMP-2 was dysregulated in preeclampsia.

Conclusions: MiR-517-5p is highly expressed in placenta samples of preeclampsia pregnancies, which could promote proliferative and invasive abilities of JAR cells by inhibiting ERK/MMP-2 pathway.