Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia

Liang, Xiaoyan; Chen, X.; Jin, Yingyu; Chen, X.O.; Chen, Q.Z.

doi:10.4238/2014.december.18.2

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…In our study, we focused on the altered expression of PEG10 in PC. During physiological conditions, adequate PEG10 expression is necessary for placental development and it has been shown that PEG10 is downregulated in case of preeclampsia [ 24 – 26 ]. PEG10 expression was later shown to be abnormally reactivated in some malignancies (such as liver cancer, lung cancer, and gallbladder cancer) and that it could be a biomarker for progression and prognosis of certain cancers [ 13 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer

Peng

Zhu

Yin

et al. 2017

J Exp Clin Cancer Res

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BackgroundOverexpression of paternally expressed gene-10 (PEG10) is known to promote the progression of several carcinomas, however, its role in pancreatic cancer (PC) is unknown. We investigated the expression and function of PEG10 in PC.MethodsPEG10 expression and correlation with PC progression was assessed in cancerous tissues and paired non-cancerous tissues. Further, the role of PEG10 in PC cell progression and the underlying mechanisms were studied by using small interfering RNA (Si-RNA).ResultsPEG10 expression was significantly higher in cancerous tissues and correlated with PC invasion of vessels and Ki-67 expression. Si-RNA mediated PEG10 knockdown resulted in inhibition of proliferation and G0/G1 cell cycle arrest, which was mediated by p21 and p27 upregulation. A decrease in PC cell invasion and migration, mediated by ERK/MMP7 pathway, was observed in PEG10 knockdown group. Further, findings of ChIP assay suggested that E2F-1 could directly enhance the expression of PEG10 through binding to PEG10 promoter.ConclusionsIn conclusion, PEG10 was identified as a prognostic biomarker for PC and E2F-1 induced PEG10 could promote PC cell proliferation, invasion, and metastasis.

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Section: Discussionmentioning

confidence: 99%

PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer

Peng

Zhu

Yin

et al. 2017

J Exp Clin Cancer Res

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“…By analyzing the parent of origin SNPs of PEG10 in 10 family trios, Metsalu et al identified that PEG10 was exclusively expressed from the paternal allele in the placenta, although the child’s blood exhibited a heterogeneous genotype in the same position, confirming the imprinting of the maternal allele of PEG10 in the human placenta [ 21 ]. Aberrant expression of PEG10 in the placenta was found clinically to be associated with several pregnancy complications [ 4 – 7 ], suggesting a potential role of PEG10 in placental development and function. In the present study, with a siRNA-mediated knockdown approach, we show that PEG10 affects trophoblast proliferation, differentiation and invasion, and that PEG10 regulates trophoblast invasion via MMP-2, MMP-9 and TIMP-1.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, examination of PEG10 levels after delivery of placentas may not reveal the pathogenic mechanism for the pregnancy complications because of the lapsed action time. For example, contradictory PEG10 levels in preeclamptic placentas were reported [ 7 , 23 ], presumably owning to the placentas at different gestation ages. In the present study, primary chorionic villi were isolated from the human placentas at a gestation age of around 7 weeks, approximately when PEG10 starts to function.…”

Section: Discussionmentioning

confidence: 99%

“…Functional study of PEG10 using a knockout mouse model has revealed its crucial role in placental development [ 3 ]. Moreover, clinical studies have reported aberrant PEG10 expression in the human placenta in multiple pregnancy complications such as spontaneous miscarriages and fetal death [ 4 , 5 ], intrauterine growth restriction [ 6 ] and preeclampsia [ 7 ]. Although PEG10 has been proposed to be a critical player during gestation, its role in normal placental development and in the pathogenesis of the pregnancy disorders remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion

et al. 2015

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Paternally expressed gene 10 (PEG10) is an imprinted and monoallelic expressed gene. Previous study using a knockout mouse model revealed a crucial role of PEG10 in placental development, yet the exact function of PEG10 during placentation remains to be elucidated. In this study, denuded chorionic villi were prepared from first trimester human placentas, and transduced with PEG10 small interference RNA (siRNA) or non-targeting control sequence by lentiviral infection. Immunohistochemical staining revealed that silencing of PEG10 in the chorionic villous explants resulted in reduced immune-reactivity to CK7, Ki67 and integrin α5, implying that silencing of PEG10 impaired the proliferation of villous trophoblasts and may interfere with the activity of extravillous trophoblasts. We further investigated the role of PEG10 in the proliferation, migration and invasion of JEG-3 trophoblast cell line and the primary chorionic villous cells. PEG10-silenced JEG-3 cells and primary chorionic villous cells displayed a reduced proliferation rate and impaired invasiveness in vitro. Silencing of PEG10 in trophoblast cells led to upregulated expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as downregulated expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, knockdown of TIMP-1 reversed the suppressed invasiveness of PEG10 siRNA-transduced JEG-3 cells. In conclusion, our study demonstrates that PEG10 plays an important role in trophoblast proliferation and promotes trophoblast invasion through TIMP-1.

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“…Double-labelled IF was used to identify CTB and STB cells in tissue sections using antibodies against two proteins: Paternally expressed gene 10 (PEG-10) and Pregnancy-specific beta-1-glycoprotein 1 (PSG-1), respectively. These proteins are expressed by CTBs (PEG-10) [35] and STBs (PSG-1) [36], allowing the two cell types to be clearly distinguished (Figure 1(a)) and purity to be confirmed (Figure 1(b)). Furthermore, double-labelled IF revealed punctate staining of both 5-mC and 5-hmC and confirmed colocalization of both markers (Figure 1(c)).…”

Section: Identification and Isolation Of Ctb And Stb Cellsmentioning

confidence: 99%

Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation

et al. 2019

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The placenta is an important organ in pregnancy, however, very little is understood about placental development at a molecular level. This includes the role of epigenetic mechanisms and how they change throughout gestation. DNA methylation studies in this organ are complicated by the different cell types that make up the placenta, each with their own unique transcriptome and epigenome. Placental dysfunction is often associated with pregnancy complications such as preeclampsia (PE). Aberrant DNA methylation in the placenta has been identified in pregnancy complications. We used immunohistochemistry (IHC) and immunofluorescence (IF) to localize 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in placenta tissue from first and second trimester as well as uncomplicated term and PE samples. IHC analysis of whole placental tissues showed 5-mC increased across gestation. When cytotrophoblasts (CTB) and syncytiotrophoblasts (STB) were isolated and assessed using IF, both 5-mC and 5-hmC increased in term CTBs compared to first/second-trimester samples. Staining intensity of 5-hmC was higher in first/second trimester STBs compared to CTBs (P = 0.0011). Finally, IHC staining of term tissue from PE and uncomplicated pregnancies revealed higher 5-mC staining intensity in placentas from PE pregnancies (P = 0.028). Our study has shown increased 5-mC and 5-hmC staining intensities across gestation and differed between two trophoblast populations. Differences in DNA methylation profiles between placental cell types may be indicative of different functions and requires further study to elucidate what changes accompany placental pathologies.

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Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia

Cited by 8 publications

References 18 publications

PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer

PEG10 overexpression induced by E2F-1 promotes cell proliferation, migration, and invasion in pancreatic cancer

Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion

Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation

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