MiR-26a-5p/EZH2 Mediates Wnt2 Promoter Methylation to Regulate Trophoblast Dysfunction

Area of Science:

• Reproductive biology
• Molecular genetics
• Cell biology

Background:

• Preeclampsia (PE) affects up to 10% of pregnancies globally.
• Understanding the molecular mechanisms of PE is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role and mechanism of microRNA-26a-5p (miR-26a-5p) in trophoblast function.
• To elucidate the miR-26a-5p/EZH2/Wnt2 signaling pathway in the context of preeclampsia.

Main Methods:

• Cell proliferation and apoptosis assays (CCK-8, colony formation, flow cytometry).
• Luciferase reporter assay to confirm miR-26a-5p and EZH2 interaction.
• Methylation-specific PCR to assess Wnt2 DNA methylation in HTR8 cells.

Main Results:

• miR-26a-5p and Wnt2 significantly promoted trophoblast proliferation and inhibited apoptosis (P<0.05).
• Both Wnt2 and miR-26a-5p suppressed inflammatory cytokine secretion (P<0.05).
• EZH2 was identified as a direct target of miR-26a-5p, and miR-26a-5p mediated Wnt2 DNA methylation, regulating Wnt2 expression.

Conclusions:

• miR-26a-5p upregulates Wnt2 expression by downregulating EZH2.
• The miR-26a-5p/EZH2/Wnt2 axis enhances trophoblast proliferation while inhibiting inflammation and apoptosis.
• This pathway represents a novel indicator for preeclampsia prevention and treatment.