Disordered p53-MALAT1 pathway is associated with recurrent miscarriage

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Cell Biology

Background:

• Recurrent miscarriage (RM) affects 1% of couples, with unknown causes in 50% of cases.
• P53, a cell cycle regulator, influences long noncoding RNA (lncRNA) expression and is overexpressed in RM patients.
• The role of p53 and lncRNAs in RM pathogenesis requires further investigation.

Purpose of the Study:

• To investigate the relationship between p53 and specific lncRNAs in recurrent miscarriage.
• To elucidate the mechanism by which p53 affects lncRNA expression and trophoblast function.

Main Methods:

• Detected p53 and six lncRNA expression levels in villous tissue from RM patients and controls.
• Utilized luciferase assays to confirm p53 binding to the MALAT1 promoter.
• Performed functional studies using human trophoblast cells (HTR-8/SVneo) with p53 and MALAT1 overexpression.

Main Results:

• NEAT1 and MALAT1 lncRNA levels were significantly reduced in RM patients.
• MALAT1 levels showed a negative correlation with p53 protein levels.
• p53 directly represses MALAT1 expression by binding to its promoter.
• p53 overexpression decreased trophoblast cell proliferation, migration, and invasion, while increasing apoptosis.
• MALAT1 overexpression partially rescued these functional deficits caused by p53 overexpression.

Conclusions:

• P53-mediated repression of MALAT1 contributes to the pathogenesis of recurrent miscarriage.
• Dysregulation of the p53-MALAT1 axis impacts trophoblast cell function, potentially leading to pregnancy loss.
• Targeting the p53-MALAT1 pathway may offer therapeutic strategies for recurrent miscarriage.