MiR-124-3p promotes trophoblast cell HTR-8/SVneo pyroptosis by targeting placental growth factor.
Placenta
; 101: 176-184, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33010604
INTRODUCTION: 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. METHODS: 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-1ß 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: 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-1ß 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. CONCLUSION: 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preeclampsia
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Trofoblastos
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MicroARNs
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Piroptosis
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Factor de Crecimiento Placentario
Tipo de estudio:
Etiology_studies
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Observational_studies
Límite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Placenta
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Países Bajos