Unraveling the impact of hsa-miR-518c-5p on placental health: mechanistic insights into preeclampsia pathogenesis.

BACKGROUND

Preeclampsia (PE), a severe hypertensive disorder during pregnancy, is characterized by dysfunctional placental trophoblasts. This study identifies hsa-miR-518c-5p as a key regulator of trophoblast differentiation and invasion, potentially implicated in PE pathology.

METHODS

In human PE placentae, the expression of hsa-miR-518c-5p was measured, revealing a significant decrease in the trophoblastic layer. Human trophoblast organoids, villous explants derived from human early villi, and HTR8/SVneo cell line were used to explore the roles of hsa-miR-518c-5p in trophoblast differentiation, migration, and invasion. RNA sequencing was conducted to analyze hsa-miR-518c-5p-mediated transcriptomic changes. Mechanistic studies were performed using western blotting, ubiquitin ligases inhibitor, and co-immunoprecipitation assays. Changes in signaling pathway were validated in human PE placentas.

RESULTS

The experiments showed that hsa-miR-518c-5p promotes the differentiation of human trophoblast organoids into extravillous trophoblasts (EVTs) and stimulates EVTs migration and invasion. Mechanistically, hsa-miR-518c-5p targets the mRNA of p120 catenin. The p120 catenin protein interacts with WISP2, protecting it from ubiquitin-mediated degradation and modulating the EMT pathway. Elevated levels of p120 catenin and WISP2 were observed in the placentae of PE patients, confirming the regulatory role of hsa-miR-518c-5p.

CONCLUSIONS

These findings underscore the importance of hsa-miR-518c-5p in determining EVTs differentiation and infiltration, suggesting its involvement in PE pathogenesis.