HDAC2-mediated proliferation of trophoblast cells requires the miR-183/FOXA1/IL-8 signaling pathway

Pre-eclampsia (PE) is a major cause of maternal and perinatal death. Previous research has indicated the role of histone deacetylase 2 (HDAC2) in the pathogenesis of PE but the relevant molecular mechanisms are unknown. However, there is hitherto little information concerning the molecular mechanism behind HDAC2 in PE. Herein, we hypothesized that HDAC2 promotes trophoblast cell proliferation and this requires the involvement of microRNA-183 (miR-183), forkhead box protein A1 (FOXA1), and interleukin 8 (IL-8). We collected placental specimens from 30 PE affected and 30 normal pregnant women. HDAC2 and FOXA1 were poorly expressed while miR-183 and IL-8 were highly expressed in placental tissues in PE. In vitro, HDAC2 overexpression enhanced the proliferation, migration, and invasion of human trophoblast cells HTR-8/SVNEO. HDAC2 inhibited the expression of miR-183 by diminishing H4 acetylation in the miR-183 promoter region. miR-183 inhibition by its specific inhibitor increased the expression of FOXA1 and thus enhanced HTR-8/SVNEO cell proliferation, migration, and invasion. FOXA1, a transcriptional factor, enhanced HTR-8/SVNEO cell proliferation, migration, and invasion by inhibiting the transcription of IL-8. We also observed HDAC2 knockdown was lost upon FOXA1 overexpression, suggesting that HDAC2 could promote HTR-8/SVNEO proliferation, migration, and invasion through the miR-183/FOXA1/IL-8 pathway. In summary, the results highlighted the role of the HDAC2/miR-183/FOXA1/IL-8 pathway in PE pathogenesis and thus suggest a novel molecular target for PE.

Automated summary

This study elucidated the important role of the HDAC2/miR-183/FOXA1/IL-8 pathway in the pathogenesis of preeclampsia, providing a novel molecular target for the treatment of PE.