ArticleCell biology and toxicology2021
Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway.
Article in Cell biology and toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 53 citations in OpenAlex.
- Regulatory mechanisms of microRNAs in reproductive toxicity induced by environmental pollutants: a mini review.Archives of toxicology · 2026Review
- Exposure to high doses of tyre antioxidant 6PPD causes senescence to induce unexplained miscarriage by suppressing BAZ1B-mediated ubiquitination degradation of P21.EBioMedicine · 2026Article
- Bisphenol B Exposure Induces Miscarriage by Suppressing Migration/Invasion and Migrasome Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lnc-HZ05 Suppresses Trophoblast Cell Migrasome Formation by Disrupting TGFβ2 Pathway in Unexplained Recurrent Miscarriage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systems toxicology integration uncovers trophoblast apoptosis as a pivotal mechanism underlying PFAS-related recurrent miscarriage.Frontiers in cell and developmental biology · 2026Article
- Manganese modulates hepatocellular carcinoma cytotoxicity and doxorubicin sensitivity in a dose dependent manner.Frontiers in oncology · 2026Article
- Lithium exposure causes ferroptosis to induce unexplained miscarriage through non-canonical MBOAT1 pathway.Nature communications · 2025Article
- Lithium Exposure Causes Trophoblast Cuproptosis by Upregulating FOXO1/STEAP4 Axis in Unexplained Miscarriage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The novelAutophagy · 2024Article
- Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease.Cell & bioscience · 2024Review
- Hypoxia causes trophoblast cell ferroptosis to induce miscarriage through lnc-HZ06/HIF1α-SUMO/NCOA4 axis.Redox biology · 2024Article
- Defective Homologous Recombination Repair By Up-Regulating Lnc-HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ferroptosis: a new hunter of hepatocellular carcinoma.Cell death discovery · 2024Review
- Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage.Particle and fibre toxicology · 2024Article
- MANF Promotes Unexplained Recurrent Miscarriages by Interacting with NPM1 and Downregulating Trophoblast Cell Migration and Invasion.International journal of biological sciences · 2024Article
- miRNA-214-3p stimulates carcinogen-induced mammary epithelial cell apoptosis in mammary cancer-resistant species.Communications biology · 2023Article
- Failure to Connect: Experimental Evidence that Benzo(a)pyrene Impedes Embryonic Implantation.Environmental health perspectives · 2023Article
- BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a NovelEnvironmental health perspectives · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
Normal pregnancy is essential for human reproduction. However, environmental BaP (benzo(a)pyrene) and its metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) induce dysfunctions of human trophoblastic cells, which could further result in miscarriage. Yet, the molecular mechanisms remain poorly understood. In this work, a novel lnc-HZ03 and a novel miR-hz03 were identified. Both lnc-HZ03 and miR-hz03 were highly expressed in human recurrent miscarriage villous tissues and in BPDE-exposed trophoblastic cells. Lnc-HZ03 and miR-hz03 upregulated each other, forming a positive feedback loop. MiR-hz03 could also upregulate p53 level by enhancing its mRNA stability. Both lnc-HZ03 and p53 mRNA contained the target site for miR-hz03 and could directly interact with miR-hz03. It was this target site instead of its mutant on lnc-HZ03 that regulated p53 expression. Subsequently, the upregulated p53 facilitated SAT1 transcription and enhanced SAT1-catalyzed spermine metabolism, which further resulted in trophoblastic cell apoptosis and induced miscarriage. All together, the p53/SAT1 pathway upregulated by lnc-HZ03 and miR-hz03 could promote BPDE-induced human trophoblastic cell apoptosis and the occurrence of miscarriage, shedding novel light on the causes of miscarriage. Graphical abstract Lnc-HZ03 and miR-hz03 regulate the occurrence of recurrent miscarriage (RM). In human trophoblastic cells, lnc-HZ03 upregulates miR-hz03 level. MiR-hz03 increases the RNA stability of lnc-HZ03 and p53 mRNA. P53 promotes SAT1 transcription and reduces its cellular spermine content, resulting in cell apoptosis. Under normal conditions, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are downregulated, maintaining normal pregnancy. After exposure to BPDE, lnc-HZ03/miR-hz03 and p53/SAT1 pathways are upregulated and finally induce miscarriage.
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