Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage

Xie, Jiayu; Liang, Tingting; Zhao, Jingsong; Xu, Zhongyan; Tian, Peng; Wang, Rong; Mi, Chenyang; Huang, Weijian; Chen, Weina; Zhang, Huidong

doi:10.1007/s10565-021-09606-z

Cited by 31 publications

(49 citation statements)

References 58 publications

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“…High-throughput mRNA sequencing was performed on HiSeq 2000 sequencing platform (BGI-Shenzhen) according to BGI commercial standard process ( https://www.bgi.com/ ). 28 , 29 , 31 Briefly, total RNAs were extracted by Trizol reagent (Thermo Fisher Scientific). The process included the removal of rRNA, synthesis of double-stranded cDNA, end repair, degradation of one strand, and enrichment of the other strand by polymerase chain reaction (PCR).…”

Section: Methodsmentioning

confidence: 99%

“… 28 Based on these sequencing data, we identified a number of novel lncRNAs of interest, including lnc-HZ01, which was found to regulate BPDE-suppressed trophoblast cell proliferation and miscarriage by forming a lnc-HZ01/MXD1 feedback loop 29 ; lnc-HZ03, which up-regulated p53/SAT1 pathway to promote trophoblast apoptosis and affected miscarriage 28 ; lnc-HZ04, which served as a ceRNA for miR-hz04 and up-regulated the

pathway 30 ; and lnc-HZ08, which regulated BPDE-induced trophoblast cell dysfunctions and was associated with miscarriage. 31 These works illustrate that these lncRNAs are closely associated with the occurrence of miscarriage. However, a large number of novel lncRNAs have yet to be identified.…”

Section: Introductionmentioning

confidence: 93%

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BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

Dai

Huang

et al. 2023

Environ Health Perspect

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Background: Recurrent miscarriage (RM) affects 1%–3% of pregnancies. However, in almost 50% of cases, the cause is unknown. Increasing evidence have shown that benzo(a)pyrene [B(a)P], a representative of polycyclic aromatic hydrocarbons (PAHs), is correlated with miscarriage. However, the underlying mechanisms of B(a)P/benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-induced trophoblast cell dysfunctions and miscarriage remain largely unknown. Objective: The objective was to discover the role(s) of a novel lncRNA, lnc-HZ09 , in the regulation of BPDE-inhibited migration and invasion of trophoblast cells and the occurrence of miscarriage. Method: Human trophoblast cells were treated with 0, 0.25, 0.5, BPDE with or without corresponding lnc-HZ09 silencing or overexpression. Using these cells, we evaluated cell migration and invasion, the mRNA and protein levels of members of the PLD1/RAC1/CDC42 pathway, the regulatory roles of lnc-HZ09 in PLD1 transcription and mRNA stability, and lnc-HZ09 transcription and stability. Human villous tissues were collected from RM ( ) group and their matched healthy control (HC, ) group. We evaluated the levels of BPDE-DNA adducts, lnc-HZ09, and the mRNA and protein expression of members of the PLD1/RAC1/CDC42 pathway, and correlated their relative expression levels. We further constructed 0, 0.05 or B(a)P-induced mouse miscarriage model (each ), in which the mRNA and protein expression of members of the Pld1/Rac1/Cdc42 pathway were measured. Results: We identified a novel lnc-HZ09 . Human trophoblast cells treated with lnc-HZ09 exhibited less cell migration and invasion. In addition, the levels of this lncRNA were higher in villous tissues from women with recurrent miscarriage than those from healthy individuals. SP1-mediated PLD1 mRNA levels were lower, and HuR-mediated PLD1 mRNA stability was less in trophoblast cells overexpressing lnc-HZ09 . However, trophoblast cells treated with MSX1 had higher levels of lnc-HZ09 , and METTL3-mediated m6A methylation on lnc-HZ09 resulted in greater lnc-HZ09 RNA stability. In BPDE-treated human trophoblast cells and in RM villous tissues, MSX1-mediated lnc-HZ09 transcription and METTL3-mediated lnc-HZ09 stability were both greater. In our mouse miscarriage model, B(a)P-treated mice had lower mRNA and protein levels of members of the Pld1/Rac1/Cdc42 pathway. Discussion: These results suggest that in human trophoblast cells, BPDE exposure up-regulated lnc-HZ09 level, suppressed PLD1/RAC1/CDC42 pathway, and inhibited migration and invasion, prov...

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

Dai

Huang

et al. 2023

Environ Health Perspect

Self Cite

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“…Additionally, benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide(BPDE), the ultimate metabolite of BaP, could induce dysfunction in trophoblasts. The expression of lnc-HZ08 was significantly upregulated in both RM tissue and BPDE-treated cells, and overexpression lnc-HZ08 suppressed the PI3K and AKT protein levels, and the downstream proteins CDK2 and p-P21 [ 52 ]. Meanwhile, lnc-HZ08 promoted the ubiquitin degradation of PI3K by promoting the interaction between CBL and PI3K in trophoblasts; therefore, lnc-HZ08 may negatively regulate proliferation, invasion and migration by inhibiting the PI3K/p-AKT/P21/CDK2 signaling pathway in BPDE-exposed trophoblasts [ 52 ].…”

Section: The Mechanism Of Lncrnas In Recurrent Miscarriagementioning

confidence: 99%

The possible role of long non-coding RNAs in recurrent miscarriage

Zhang

2022

Mol Biol Rep

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Recurrent miscarriage (RM) is a complicated disease in reproductive medicine that impacts many families. Currently, the etiology of RM is thought to include chromosome abnormalities, reproductive tract malformations, autoimmune dysfunction, infection, and environmental factors. However, the underlying mechanisms of RM remain unknown. At present, research on long non-coding RNAs (lncRNAs) is rapidly emerging and becoming a hot research topic in epigenetic studies. Recent studies revealed that lncRNAs are strongly linked to RM and play a crucial role in epigenetic, cell cycle, cell differentiation regulation, and other life activities. This article mainly reviews the difference in lncRNA expression in patients with RM and regulation of susceptibility, endometrial receptivity, and the maternal-fetal interface. Meanwhile, the correlation between lncRNAs and RM is expounded, which provides new insights for the early diagnosis and treatment of RM.

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“…Xie et al found that the DNA methylation of lncHZ08 promoter was decreased in the decidua of RPL, and the estrogen receptor (ER)-mediating the transcription of lncHZ08 was increased. The up-regulated lncHZ08 inhibits the PI3K/p-AKT/p-P21/CDK2 pathway by down-regulating PI3K, thereby reducing the proliferation, migration and invasion of trophoblast cells, and further inducing the occurrence of abortion (118). Fatima et al analyzed the causal relationship between methyltransferase, methylation and cell apoptosis in abortion through structural equation modeling (119).…”

Section: Dna Methylation Of Placenta/ Decidual and Rplmentioning

confidence: 99%

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Zhou

Xiong

et al. 2021

Front. Immunol.

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Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

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Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage

Cited by 31 publications

References 58 publications

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

The possible role of long non-coding RNAs in recurrent miscarriage

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

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