MiR-124-3p promotes trophoblast cell HTR-8/SVneo pyroptosis by targeting placental growth factor

MiR-124-3p is one of the aberrantly expressed miRNAs in the placentas of patients with preeclampsia (PE), a severe obstetric complication characterised by hypertension and proteinuria. This study aimed to investigate the role of miR-124-3p in the invasion, migration and death of trophoblast cells and explore the potential mechanisms.

MiR-124-3p expression in placental tissues was compared with that in normal placenta. HTR8/SVneo cells were then transfected with miR-124-3p mimics to examine cellular apoptosis, migration and invasion. Furthermore, the expression of pyroptosis-related molecular NLRP3, Pro-caspase1, caspase1, IL-1β and GSDMD was examined with Western blot. Dual luciferase reporter assay was performed to confirm that placental growth factor (PLGF) is a direct target of miR-124-3p, and HTR-8/SVneo cells were transfected with small interfering RNA PLGF (siPLGF) to determine whether PLGF knockdown promotes HTR-8/SVneo pyroptosis. Finally, intracellular ROS was diminished with N-acetyl-l-cysteine (NAC) to observe whether the pro-pyroptosis effect of PLGF knockdown is alleviated.

Results in this study showed that miR-124-3p expression was remarkably increased in the placenta of patients with PE. Moreover, the transfection of miR-124-3p mimics in trophoblastic cells significantly decreased cell migration and invasion but increased cell apoptosis and the expression of NLRP3, pro-caspase1, caspase1, IL-1β and GSDMD. Therefore, PLGF was confirmed as a direct target of miR-124-3p. Finally, siPLGF transfection can mimic the effects of miR-124-3p, and NAC can inhibit this effect.

In summary, miR-124-3p is upregulated in PE, and in vitro functional analysis revealed that this mRNA inhibits trophoblast invasion and migration but promotes cell pyroptosis partly via the PLGF-ROS pathway.