LncRNA-ATB Contributes to Severe Preeclampsia by Modulating the p53/MDM2 Pathway via PABPC1
- PMID: 40558399
- DOI: 10.1096/fj.202500351R
LncRNA-ATB Contributes to Severe Preeclampsia by Modulating the p53/MDM2 Pathway via PABPC1
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.
© 2025 Federation of American Societies for Experimental Biology.
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References
-
- E. A. Phipps, R. Thadhani, T. Benzing, and S. A. Karumanchi, “Pre‐Eclampsia: Pathogenesis, Novel Diagnostics and Therapies,” Nature Reviews. Nephrology 15, no. 5 (2019): 275–289.
-
- A. R. Bouter and J. J. Duvekot, “Evaluation of the Clinical Impact of the Revised ISSHP and ACOG Definitions on Preeclampsia,” Pregnancy Hypertension 19 (2020): 206–211.
-
- A. C. Staff, H. E. Fjeldstad, I. K. Fosheim, et al., “Failure of Physiological Transformation and Spiral Artery Atherosis: Their Roles in Preeclampsia,” American Journal of Obstetrics and Gynecology 226, no. 2s (2022): S895–S906.
-
- S. Greenbaum, I. Averbukh, E. Soon, et al., “A Spatially Resolved Timeline of the Human Maternal‐Fetal Interface,” Nature 619, no. 7970 (2023): 595–605.
-
- S. M. Ali and R. A. Khalil, “Genetic, Immune and Vasoactive Factors in the Vascular Dysfunction Associated With Hypertension in Pregnancy,” Expert Opinion on Therapeutic Targets 19, no. 11 (2015): 1495–1515.
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