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. 2025 Jun 30;39(12):e70736.
doi: 10.1096/fj.202500351R.

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

Jiashuo Zhang  1 , Lan Mei  2 , Yanping Zhang  1 , Xiaohong Wei  1 , Min Liu  1 , Yangxue Yin  1 , Qin Xu  1 , Lingyun Liao  1 , Linbo Gao  3 , Rong Zhou  1
Affiliations

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

Jiashuo Zhang et al. FASEB J. .

Abstract

Abnormal spiral artery remodeling is the starting point of preeclampsia. Placental lncRNA-ATB levels are significantly reduced in patients with severe preeclampsia (sPE), and these reduced levels can inhibit the biological functions of HTR-8/SVneo trophoblasts. However, the mechanism by which lncRNA-ATB regulates the biological behavior of trophoblasts remains unclear. Here, we aimed to identify proteins that interact with lncRNA-ATB in trophoblasts and uncover the biological regulatory mechanism associated with this molecule. In this study, RNA-protein pull-down and RNA immunoprecipitation tests were used to identify lncRNA-ATB downstream factors. Poly(A)-binding protein cytoplasmic 1 (PABPC1) was a target protein of lncRNA-ATB, and its expression was positively regulated by lncRNA-ATB in trophoblasts. Reduced PABPC1 expression inhibited proliferation, migration, invasion, and tube formation, and enhanced apoptosis in trophoblast cells. In sPE-affected placentas, PABPC1 expression was reduced, which may have mediated the effect of lncRNA-ATB on MDM2. Moreover, MDM2 expression was inhibited after lncRNA-ATB or PABPC1 knockdown in trophoblasts, and reduced MDM2 expression suppressed trophoblast biological functions. Further, the interaction between PABPC1 and MDM2 was suggested to be mediated by p53, and p53 expression was negatively regulated by PABPC1. In summary, PABPC1 mediates the effects of lncRNA-ATB on trophoblast biological functions via the p53/MDM2 pathway. Our findings provide a new perspective on the role of lncRNA-ATB in sPE pathogenesis.

Keywords: MDM2; PABPC1; lncRNA‐ATB; severe preeclampsia; trophoblast.

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