Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.
Mol Hum Reprod
; 30(6)2024 May 30.
Article
in En
| MEDLINE
| ID: mdl-38704863
ABSTRACT
Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uterine Contraction
/
Methyl-CpG-Binding Protein 2
/
Obstetric Labor, Premature
/
Myometrium
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Mol Hum Reprod
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA REPRODUTIVA
Year:
2024
Document type:
Article
Affiliation country:
China