Abstract: Objective To investigate the effects of microRNA-34a (miR-34a) targeting matrix metalloproteinase 2 (MMP2) on the migration and invasion of human villous trophoblasts HTR-8/SVneo induced by tumor necrosis factor- α (TNF-α). Methods Human villous trophoblasts HTR-8/SVneo cells were cultured in vitro and stimulated with 0.5 μg/L TNF-α. Cells were divided into the control group, the TNF-α induction group, the NC group, the miR-34a mimics group, the iNC group and the miR-34a inhibitor group. The expression levels of miR-34a and MMP2 mRNA were detected by quantitative real time-PCR (qRT-PCR). The cell proliferation, invasion and migration were detected by cell counting kit 8 (CCK-8), transwell assay and scratch test. The expression of MMP2 protein was detected by Western blot assay. Luciferase reporter assay was used to prove the targeting relationship between miR-34a and MMP2. Results Compared with the control group, the expression level of miR-34a and the inhibition rate of cell proliferation were significantly increased in the TNF-α induction group (P＜0.05), and the expression levels of MMP2 mRNA and protein, the cell invasion number and the cell migration rate were significantly decreased (P＜0.05). Compared with the TNF-α induction group and NC group, the expression levels of miR-34a and the inhibition rate of cell proliferation were significantly increased in the miR-34a mimics group (P＜0.05), the expression levels of MMP2 mRNA and protein, the number of cell invasion and the cell migration rate were significantly decreased (P＜0.05). Compared with the TNF-α induction group and iNC group, the expression level of miR-34a and the inhibition rate of cell proliferation were significantly decreased in the miR-34a inhibitor group (P＜0.05), and the expression levels of MMP2 mRNA and protein, the number of cell invasion and the cell migration rate were significantly increased (P＜0.05). There was a targeting relationship between miR-34a and MMP2. Conclusion miR-34a may inhibit the invasion and migration of TNF-α induced human villous trophoblasts HTR-8/SVneo by negatively regulating the expression of MMP2.

Key words: microRNAs, matrix metalloproteinase 2, tumor necrosis factor-alpha, human villous trophoblasts, preeclampsia, miR-34a