1. Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop.
- Author
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Huang, Xinying, Ma, Chenglong, Huang, Wenxin, Dai, Mengyuan, Yang, Jingjing, Xu, Xiaole, Deng, Yuanlv, Yang, Yang, and Zhang, Huidong
- Subjects
TROPHOBLAST ,RECURRENT miscarriage ,APOPTOSIS ,TRANSCRIPTION factors ,MISCARRIAGE ,HUMAN beings - Abstract
Human trophoblast cell apoptosis may induce miscarriage. Trophoblast cells are sensitive to environmental BaP-7,8-dihydrodiol-9,10-epoxide (BPDE). However, how BPDE induces human trophoblast cell apoptosis is still largely elusive. In this work, we used BPDE-treated human trophoblast cells and villous tissues collected from recurrent miscarriage and health control groups to explore the underlying mechanism of BPDE-induced human trophoblast cell apoptosis. Continued with our recent work, we found that lncRNA HZ01 (lnc-HZ01) could induce human trophoblast cell apoptosis. In mechanism, lnc-HZ01 up-regulated p53 expression level by suppressing its MDM2-mediated proteasomal degradation. Meanwhile, we found that p53 acted as lnc-HZ01 transcription factor and promoted lnc-HZ01 transcription. Thus, lnc-HZ01 and p53 composed a positive feedback loop in human trophoblast cells. In normal trophoblast cells, relatively low levels of lnc-HZ01 and p53 suppressed p53/caspase-3 apoptosis pathway, giving normal pregnancy. Upon BPDE exposure, BPDE up-regulated the expression levels of lnc-HZ01 and p53, triggered this positive feedback loop, activated the p53/caspase-3 apoptosis pathway, and then induced miscarriage. Collectively, we discovered new mechanism by which lnc-HZ01 regulated BPDE-induced human trophoblast cell apoptosis, providing scientific basis for the diagnosis and treatment of unexplained recurrent miscarriage. • Lnc-HZ01 activates p53/caspase-3 pathway and induces human trophoblast cell apoptosis. • Lnc-HZ01 and p53 compose a positive feedback loop in human trophoblast. • BPDE up-regulates lnc-HZ01 and p53 expression and triggers this positive feedback loop. • Human trophoblast cell apoptosis may induce miscarriage. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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