Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop
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 villo...
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Elsevier
2022-06-01
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Series: | Ecotoxicology and Environmental Safety |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322004043 |
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author | Xinying Huang Chenglong Ma Wenxin Huang Mengyuan Dai Jingjing Yang Xiaole Xu Yuanlv Deng Yang Yang Huidong Zhang |
author_facet | Xinying Huang Chenglong Ma Wenxin Huang Mengyuan Dai Jingjing Yang Xiaole Xu Yuanlv Deng Yang Yang Huidong Zhang |
author_sort | Xinying Huang |
collection | DOAJ |
description | 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. |
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language | English |
last_indexed | 2024-04-12T16:34:51Z |
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series | Ecotoxicology and Environmental Safety |
spelling | doaj.art-9c840f5522c74b329f10bbbfcee2e3fa2022-12-22T03:25:01ZengElsevierEcotoxicology and Environmental Safety0147-65132022-06-01237113564Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loopXinying Huang0Chenglong Ma1Wenxin Huang2Mengyuan Dai3Jingjing Yang4Xiaole Xu5Yuanlv Deng6Yang Yang7Huidong Zhang8Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaResearch Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, ChinaDepartment of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China; Corresponding author at: Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China.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.http://www.sciencedirect.com/science/article/pii/S0147651322004043Environmental BaP or BPDENon-coding lncRNA-HZ01Female trophoblast cell apoptosisMDM2/p53/caspase-3Miscarriage |
spellingShingle | Xinying Huang Chenglong Ma Wenxin Huang Mengyuan Dai Jingjing Yang Xiaole Xu Yuanlv Deng Yang Yang Huidong Zhang Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop Ecotoxicology and Environmental Safety Environmental BaP or BPDE Non-coding lncRNA-HZ01 Female trophoblast cell apoptosis MDM2/p53/caspase-3 Miscarriage |
title | Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop |
title_full | Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop |
title_fullStr | Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop |
title_full_unstemmed | Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop |
title_short | Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop |
title_sort | environmental bpde induced human trophoblast cell apoptosis by up regulating lnc hz01 p53 positive feedback loop |
topic | Environmental BaP or BPDE Non-coding lncRNA-HZ01 Female trophoblast cell apoptosis MDM2/p53/caspase-3 Miscarriage |
url | http://www.sciencedirect.com/science/article/pii/S0147651322004043 |
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