Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage
Abstract: Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage ; day:29 ; month:01 ; year:2024 ; extent:22
Advanced science ; (29.01.2024) (gesamt 22)
- Creator
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Chen, Weina
Mi, Chenyang
Zhang, Ying
Yang, Yang
Huang, Wenxin
Xu, Zhongyan
Zhao, Jingsong
Wang, Rong
Wang, Manli
Wan, Shukun
Wang, Xiaoqing
Zhang, Huidong
- DOI
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10.1002/advs.202207435
- URN
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urn:nbn:de:101:1-2024013014202042758790
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:37 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Chen, Weina
- Mi, Chenyang
- Zhang, Ying
- Yang, Yang
- Huang, Wenxin
- Xu, Zhongyan
- Zhao, Jingsong
- Wang, Rong
- Wang, Manli
- Wan, Shukun
- Wang, Xiaoqing
- Zhang, Huidong
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Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage
Elevated histone demethylase KDM5C increases recurrent miscarriage risk by preventing trophoblast proliferation and invasion
Defective homologous recombination DNA repair as therapeutic target in advanced chordoma
Defective homologous recombination DNA repair as therapeutic target in advanced chordoma
Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression
Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Correction: Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors
Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling
TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway
Molecular breeding of sporeless strains of Pleurotus ostreatus using a non-homologous DNA end-joining defective strain
Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage
Elevated histone demethylase KDM5C increases recurrent miscarriage risk by preventing trophoblast proliferation and invasion
Defective homologous recombination DNA repair as therapeutic target in advanced chordoma
Defective homologous recombination DNA repair as therapeutic target in advanced chordoma
Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression
Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Correction: Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors
The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors
Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling
TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway