Pre-eclampsia (PE), a pregnancy-associated disorder, is a major contributor to maternal mortality and morbidity worldwide. Recently, microRNAs (miRNAs) were found to be associated with the pathogenesis of PE. The present study investigated the function of miR-299 in HTR-8/SVneo trophoblast cells and explored its underlying mechanism in the pathogenesis of PE. The miR-299 and histone deacetylase 2 (HDAC2) mRNA expression levels were determined by quantitative real-time PCR. Transwell invasion and wound healing assays were used to measure cell invasive and migratory ability. Luciferase reporter assay was performed to confirm the downstream targets of miR-299. Western blot was performed to measure the protein expression of HDAC2. The expression level of miR-299 in placental tissues from pregnant women with severe PE was significantly higher than that from normal pregnant women. MiR-299 overexpression suppressed the invasion and migration of trophoblast cells; and knock-down of miR-299 promoted the invasion and migration of trophoblast cells. Bioinformatics prediction and luciferase reporter assay confirmed that miR-299 directly targeted the 3' untranslated region of HDAC2. The mRNA expression level of HDAC2 in placental tissues from pregnant women with severe PE was significantly lower than that from normal pregnant women, and was negatively correlated the expression level of miR-299 in placental tissues from pregnant women with severe PE. HDAC2 siRNA transfection suppressed the mRNA and protein expression levels of HDAC in trophoblast cells compared with control group, and HDAC2 siRNA transfection also suppressed the trophoblast cell invasion and migration compared with control group. Enforced expression of HDAC2 in trophoblast cells attenuated the inhibitory effects of miR-299 overexpression on cell invasion and migration. In summary, the results showed the up-regulation of miR-299 in the placental tissues from women with severe PE and miR-299 suppressed the invasion and migration of trophoblast cells partly via targeting HDAC2.
Keywords: HDAC2; Invasion; MiR-299; Migration; Pre-eclampsia; Trophoblast.
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