Elevated miR-23a impairs trophoblast migration and invasiveness through HDAC2 inhibition and NF-κB activation

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the onset of hypertension and proteinuria with onset after the 20th week of gestation. The pathogenesis of PE is attributed to increased trophoblast cell death and poor trophoblast migration/invasiveness. This study investigates the function of microRNA-23a (miR-23a) in PE and its effects on migration and invasion of trophoblast cells HTR-8/SVneo. We found higher expression of miR-23a in placental tissue samples from PE pregnant women compared to samples from normal pregnant women. Enhancing miR-23a expression by its specific mimic reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis. The dual-luciferase reporter gene assay revealed miR-23a binding with HDAC2. We found that HDAC2 was poorly expressed in placental tissue samples from PE pregnant women, and its expression correlated inversely with miR-23a expression. HTR-8/SVneo cells showed diminished HDAC2 expression upon miR-23a elevation and increased HDAC2 expression upon miR-23a inhibition. Lentivirus-mediated HDAC2 knockdown mimicked the effects of miR-23a on HTR-8/SVneo cells and led to NF-κB activation. Similarly, HDAC2 overexpression and NF-κB inhibition both abrogated the effects of miR-23a on HTR-8/SVneo cells, suggesting that miR-23a reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis by HDAC2 inhibition and NF-κB activation. In summary, these results support a novel role of miR-23b in invasion and apoptosis of trophoblast cells, and imply that targeting miR-23b may be a new avenue for treating PE.