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

Preeclampsia (PE) is a common complication of pregnancy, with a concomitant incidence rate of up to 10% among pregnant women worldwide.

In the current research, we explored the role and mechanism of miR-26a-5p in trophoblast function using CCK-8, colony formation assay, and flow cytometry. The interaction between miR-26a-5p and EZH2 was analyzed using a luciferase reporter assay. Methylationspecific PCR was performed to detect the methylation level of Wnt2 in HTR8 cells.

Wnt2 and miR-26a-5p promoted the proliferation and inhibited the apoptosis in trophoblasts (P<0.05). The secretion of inflammatory cytokines was suppressed by Wnt2 and miR-26a-5p (P<0.05). EZH2 was identified as a regulatory target of miR-26a-5p using HTR8 cells and bioinformatic tools. miR-26a-5p inhibited expression through direct binding to EZH2. Importantly, miR- 26a-5p mediated DNA methylation of Wnt2 to regulate Wnt2 expression in HTR8 cells.

This study elucidates a novel regulatory axis that alleviates trophoblast dysfunction by promoting proliferation and suppressing inflammation and apoptosis. The findings reveal that the miR-26a-5p/EZH2/Wnt2 pathway, potentially involving promoter methylation, is crucial for maintaining trophoblast function. This work identifies a promising therapeutic target for PE, although further in vivo validation is required to confirm its clinical potential.

It was found that miR-26a-5p increased the expression of Wnt2 by downregulating EZH2. Moreover, miR-26a-5p/EZH2/Wnt2 promoted the proliferation and inhibited the inflammation and apoptosis in trophoblasts. This research provides insight into the role of miR-26a- 5p/EZH2/Wnt2 as a novel indicator for the prevention and treatment of PE.