miR-526b-5p/c-Myc/Foxp1 participates in recurrent spontaneous abortion by regulating the proliferation, migration, and invasion of trophoblasts.
J Assist Reprod Genet
; 40(7): 1559-1572, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37052757
ABSTRACT
PURPOSE:
As a member of the C19MC family, miR-526b-5p is mainly expressed in the placental tissue and is a well-known tumor suppressor microRNA. However, its effect on the function of trophoblasts and its role in the development of recurrent spontaneous abortion (RSA) remains unclear.METHODS:
Transcriptome sequencing, quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, 5-ethynyl-2'-deoxyuridine (Edu) proliferation analysis, cell counting kit-8 (CCK8) assay, Transwell assays, and wound healing were used to detect the proliferation, migration, and invasion capacity of trophoblasts. Target genes of miR-526b-5p were obtained by the dual luciferase reporter system. The promoter-reporter system and ChIP-qPCR were used to prove that c-Myc positively regulated the expression of Foxp1RESULTS:
The miR-526b-5p levels were significantly higher in patients with RSA than in controls. High expression of miR-526b-5p inhibited the proliferation, migration, and invasion of trophoblast cell line. By contrast, low expression of miR-526b-5p promoted the proliferation and migration of trophoblast cell line. Target genes of miR-526b-5p were c-Myc and Foxp1. c-Myc positively regulated the expression of Foxp1 by binding to the Foxp1 promoter location -146/-135. Finally, miR-526b-5p impeded the proliferation, migration, and invasion of trophoblasts by negatively regulating c-Myc by rescue experiments.CONCLUSION:
Thus, miR-526b-5p affected the proliferation, migration, and invasion of trophoblasts by targeting c-Myc and Foxp1. Low expression of c-Myc further deactivated the positive transcriptional regulation of c-Myc on Foxp1, which may be the mechanism of RSA. This study provides potential therapeutic targets and clues for the diagnosis and treatment of RSA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aborto Habitual
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Proteínas Proto-Oncogênicas c-myc
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MicroRNAs
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Fatores de Transcrição Forkhead
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
J Assist Reprod Genet
Assunto da revista:
GENETICA
/
MEDICINA REPRODUTIVA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China