Altered DNA methylation and transcription of WNT2 and DKK1 genes in placentas associated with early-onset preeclampsia

Zhang, Linlin; Leng, Maodong; Li, Yingying; Yang, Yuan; Yang, Bo; Li, Ying; Yuan, Erfeng; Shi, Wei; Yan, Shujun; Cui, Shihong

doi:10.1016/j.cca.2018.12.026

Cited by 11 publications

(9 citation statements)

References 36 publications

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“…WNT2 gene is found to be decreased expressed in the preeclampsia placentas [14]. A recent study also confirms that reduced WNT2 expression may be implicated in the development of early-onset preeclampsia [15]. Furthermore, increasing studies have revealed the key roles of the Wnt pathway in multiple physiological and pathological processes, such as proliferation, apoptosis, differentiation, and migration [16,17].…”

Section: Introductionmentioning

confidence: 82%

Involvement of WNT2 in trophoblast cell behavior in preeclampsia development

Liu

Huang

et al. 2020

Cell Cycle

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This study aimed to determine the WNT2 expression in patients with severe preeclampsia and to explore the function of WNT2 dysregulation on the biological behaviors of trophoblast cells. The WNT2 and β-catenin expression in the patients with early-onset and late-onset severe preeclampsia and normal controls was determined. Subsequently, WNT2 was overexpressed and knocked down in HTR8 cells and WNT2 signaling pathway in regulating trophoblast cell proliferation, migration, invasion, and apoptosis were evaluated in vitro. The mRNA and protein expression levels of WNT2 and β-catenin were decreased in patients with preeclampsia, especially early-onset severe preeclampsia. Overexpression of WNT2 promoted trophoblast cell proliferation, migration, and invasion and inhibited apoptosis in vitro, whereas knockdown of WNT2 had opposite effects. The findings of this study reveal that WNT2 and β-catenin were decreased expressed in patients with preeclampsia. Decreased expression of WNT2 may inhibit trophoblast cell proliferation, migration, and invasion but induced apoptosis. WNT2 may serve as a promising biomarker for early detection of preeclampsia.

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Section: Introductionmentioning

confidence: 82%

Involvement of WNT2 in trophoblast cell behavior in preeclampsia development

Liu

Huang

et al. 2020

Cell Cycle

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“…There is some limited evidence showing methylation also contributes to the TF-gene regulations in PE. Altered DNA methylation and transcription of WNT2 and DKK1 genes in placentas are associated with PE [14]. In our analysis, the pattern of We systematically analyzed the regulation patterns of methTDMs in PE and majorly defined six kinds of patterns including relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, more and more studies focus on epigenetic patterns of PE. Lang et al suggest altered DNA methylation and transcription of WNT2 and DKK1 genes in placentas are associated with early-onset PE [14]. PE is associated with hypermethylation of IGF-1 promoter mediated by DNMT1 [15].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

Zhao

et al. 2020

Hum Genomics

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Background: Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylationmediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described. Methods: Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions. Results: The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH. Conclusion: Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

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“…The expression pattern of miR-146a-5p in PE is controversial and its biological functions remain to be investigated. Wnt2, one of the Wnt ligands, is a secreted glycoprotein downregulated in PE placentae [ 16 ]. Wnt2 is elucidated to promote the proliferation and migration of first trimester trophoblast cells via activating Wnt/β-catenin pathway [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

et al. 2021

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Objective This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Methods Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Results Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. Conclusion miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

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Altered DNA methylation and transcription of WNT2 and DKK1 genes in placentas associated with early-onset preeclampsia

Cited by 11 publications

References 36 publications

Involvement of WNT2 in trophoblast cell behavior in preeclampsia development

Involvement of WNT2 in trophoblast cell behavior in preeclampsia development

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

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