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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>These findings underscore the importance of hsa-miR-518c-5p in determining EVTs differentiation and infiltration, suggesting its involvement in PE pathogenesis.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Lu Chen,
  • Qiuling Jie,
  • Wenqian Jiang,
  • Zhixing Cheng,
  • Lingzhe Zhang,
  • Menglan Pang,
  • Yuyan Wang,
  • Liping Huang,
  • Mei Zhong,
  • Yanlin Ma,
  • Xiaojing Yue

摘要

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.