The Dysregulation of microRNA-30b Directly Regulates Cystathionine Gamma-Lyase and Exhibits Poor Invasion Activity in Preeclampsia.

Background and objective Preeclampsia (PE) is a severe pregnancy complication characterized by high blood pressure and proteinuria after 23 weeks of gestation. Insufficient trophoblast invasion has been linked to its development. Hydrogen sulfide (H₂S), with its genes cystathionine gamma-lyase (CTH) playing the role of an important vasodilator, may be associated with various diseases including PE. This study investigated the role of microRNA-30b (miR-30b) in trophoblast invasion using HTR-8/SVneo cells, blood, and placental samples Methods The study involved samples from 40 preeclamptic subjects and 40 healthy controls. Gene expression was analyzed via quantitive real-time PCR and enzyme-linked immunosorbent assay (ELISA). The effects of H₂S were simulated using a sodium hydrogen sulfide (NaHS) inhibitor (AOAA), and miR-30b inhibitors were used to assess changes in invasion capacity. Results NaHS treatment enhanced trophoblast invasion, and hypoxia/reoxygenation (H/R) + NaHS-treated cells showed increased invasion compared to H/R-treated cells alone. miR-30b inhibition led to higher expression of CTH, matrix metalloproteinase-9 (MMP-9), and reduced tissue inhibitor of metalloproteinases 1 (TIMP-1) and TIMP-2 expression, improving cell invasion. Patient samples showed lower CTH, MMP-2, and MMP-9 levels in PE, with elevated TIMP-1 and TIMP-2. Protein expression also revealed reduced CTH and MMP-9 in preeclamptic patients. Conclusions Based on our findings, miR-30b influences trophoblast invasion by modulating CTH expression and the MMP/TIMP balance. Enhanced H₂S production improves invasion, suggesting that miR-30b and related pathways can be potential therapeutic targets for PE management.