LncRNA-ATB Contributes to Severe Preeclampsia by Modulating the p53/MDM2 Pathway via PABPC1

Area of Science:

• Obstetrics and Gynecology
• Molecular Biology
• Cell Biology

Background:

• Abnormal spiral artery remodeling initiates preeclampsia (PE).
• Reduced placental long non-coding RNA ATB (lncRNA-ATB) levels are observed in severe PE (sPE) and inhibit trophoblast cell functions.
• The precise mechanism of lncRNA-ATB's regulation of trophoblast behavior is not fully understood.

Purpose of the Study:

• To identify proteins interacting with lncRNA-ATB in trophoblasts.
• To elucidate the biological regulatory mechanism of lncRNA-ATB in trophoblast function.
• To investigate the role of lncRNA-ATB in the pathogenesis of sPE.

Main Methods:

• RNA-protein pull-down assays.
• RNA immunoprecipitation (RIP) assays.
• In vitro studies involving trophoblast cell lines with lncRNA-ATB and PABPC1 knockdown.

Main Results:

• Poly(A)-binding protein cytoplasmic 1 (PABPC1) was identified as a direct downstream target of lncRNA-ATB, with its expression positively regulated by lncRNA-ATB.
• Reduced PABPC1 expression impaired trophoblast proliferation, migration, invasion, and tube formation, while enhancing apoptosis.
• PABPC1 expression was reduced in sPE placentas, potentially mediating lncRNA-ATB's effects on MDM2 via the p53/MDM2 pathway, where PABPC1 negatively regulates p53.

Conclusions:

• PABPC1 acts as a crucial mediator for lncRNA-ATB's influence on trophoblast biological functions.
• The lncRNA-ATB/PABPC1 axis regulates trophoblast behavior through the p53/MDM2 signaling pathway.
• These findings provide novel insights into the molecular mechanisms underlying lncRNA-ATB's role in severe preeclampsia pathogenesis.