scholarly journals Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

2018 ◽  
Vol 45 (3) ◽  
pp. 1013-1022 ◽  
Author(s):  
Ting Zhong ◽  
Jiaxiang Chen ◽  
Yan Ling ◽  
Bei Yang ◽  
Xingxing Xie ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Normal Pregnancy ◽  
Neuropathy Target Esterase ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Human Trophoblast ◽  
Expression Levels ◽  
Transfection Method ◽  
Underlying Mechanisms

Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

scholarly journals Down-regulation of lncRNA-NEF indicates poor prognosis in intrahepatic cholangiocarcinoma

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhanqiang Liang ◽  
Bingshuai Zhu ◽  
Dongdong Meng ◽  
Xiwen Shen ◽  
Xuemin Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Intrahepatic Cholangiocarcinoma ◽  
Plasma Levels ◽  
Migration And Invasion ◽  
Healthy Controls ◽  
Cancer Cell Migration ◽  
Down Regulation ◽  
Expression Levels ◽  
Tumor Tissues

Abstract LncRNA-NEF is a tumor suppressor lncRNA in liver cancer. The present study aimed to investigate the role of lncRNA-NEF in intrahepatic cholangiocarcinoma (IHCC), which is second most common type of primary cancer of the hepatobiliary system that causes high mortality rate. In the present study we found that lncRNA-NEF was down-regulated, while Runt-related transcription factor 1 (RUNX1) was up-regulated in tumor tissues than in adjacent healthy tissues of IHCC patients. Expression levels of lncRNA-NEF and RUNX1 were significantly and reversely correlated in tumor tissues but not in adjacent healthy tissues. Plasma levels of lncRNA-NEF were significantly lower in IHCC patients than in healthy controls. Down-regulation of lncRNA-NEF effectively distinguished stage I and II IHCC patients from healthy controls. Patients were followed up for 5 years, patients with high plasma levels of lncRNA-NEF showed significantly better survival conditions compared with patients with low expression levels of lncRNA-NEF. LncRNA-NEF overexpression led to inhibited expression of RUNX1 in cells of IHCC cell lines and inhibited cancer cell migration and invasion. In contrast, RUNX1 overexpression showed no significant effects on lncRNA-NEF expression, but attenuated the effects of lncRNA-NEF overexpression on cancer cell migration and invasion. We therefore concluded that lncRNA-NEF participated in IHCC possibly by interacting with RUNX1.

scholarly journals Silencing of the TROP2 gene suppresses proliferation and invasion of hepatocellular carcinoma HepG2 cells

2019 ◽  
Vol 47 (3) ◽  
pp. 1319-1329 ◽  
Author(s):  
Jian Zhang ◽  
Hai Ma ◽  
Liu Yang ◽  
Hongchun Yang ◽  
Zhenxing He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Human Trophoblast ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Proliferation And Invasion

Objectives Overexpression of human trophoblast cell surface antigen 2 (Trop2) has been observed in many cancers; however, its roles in proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) remain unclear. Thus, this study aimed to characterize the function of Trop2 in HCC. Methods Trop2 protein expression was detected by immunohistochemistry in HCC tissues. Cell proliferation, apoptosis, and invasion were respectively measured by CCK-8, flow cytometry, Transwell, and wound healing assays. Expression levels of epithelial–mesenchymal transition-related proteins and Trop2 protein in HCC cell lines were detected by western blotting after silencing of the TROP2 gene. Results Trop2 protein was highly expressed in HCC tissues and HCC cell lines. Trop2 mRNA and protein expression levels decreased in HepG2 and HCCLM3 cells after transfection with Trop2 siRNA. Silencing of the TROP2 gene in HepG2 and HCCLM3 cells strongly inhibited cell proliferation and migration, while enhancing cell apoptosis. Investigation of the molecular mechanism revealed that silencing of the TROP2 gene suppressed epithelial–mesenchymal transition of HepG2 and HCCLM3 cells. Conclusions The results of the present study may improve understanding of the role of Trop2 in regulation of cell proliferation and invasion, and may aid in development of novel therapy for HCC.

scholarly journals Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiayu Wang ◽  
Jinli Ding ◽  
Sainan Zhang ◽  
Xin Chen ◽  
Sisi Yan ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Recurrent Miscarriage ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Mrna Levels ◽  
Human Trophoblast ◽  
Mesenchymal Transition ◽  
Multiple Tumor

An appropriate development of the placenta consisting of trophoblast cell migration, invasion, proliferation, and apoptosis, is essential to establishing and maintaining a successful pregnancy. Ubiquitin‐specific protease 2a (USP2a) regulates the processes of metastasis in multiple tumor cells. Yet, no known research has focused on exploring the effect of USP2a on trophoblasts and its possible mechanism in the pathogenies of recurrent miscarriage (RM). In this study, we first detected the decreased mRNA levels and the protein levels of USP2a in placental villous tissue samples from the RM patients. In vitro assays verified that overexpression of USP2a promoted human trophoblast proliferation, migration, invasion, whereas knockdown of USP2a inhibited these processes. Mechanistically, USP2a activated PI3K/Akt/GSK3β signaling pathway to promote nuclear translocation of β‐catenin and further activated epithelial-mesenchymal transition (EMT) in the trophoblasts. Moreover, transforming growth factor-beta (TGF-β) up-regulated USP2a expression in trophoblasts. Interestingly, M2 macrophage secreted TGF-β induced trophoblast migration and invasion, and an anti-TGF-β antibody alleviated this effect. Collectively, this study indicated that USP2a regulated trophoblast invasion and that abnormal USP2a expression might lead to aberrant trophoblast invasion, thus contributing to RM.

scholarly journals miR-183-5p suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting MMP-9 in preeclampsia

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Mingli Suo ◽  
Yanfei Sun ◽  
Hailan Yang ◽  
Jing Ji ◽  
Yinfang He ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Cell Invasion ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Trophoblast Cells ◽  
Down Regulation ◽  
Invasion And Migration ◽  
Potential Biomarker ◽  
And Migration

Abstract Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.

scholarly journals Cross Sectional Study of Zinc, Copper and Magnesium Levels in Preeclampsia and Normal Pregnancy

2021 ◽  
Vol 8 (10) ◽  
pp. 33-36
Author(s):  
Balaji B R ◽  
K N Pujari
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Pregnant Women ◽  
Normal Pregnancy ◽  
Cross Sectional Study ◽  
Trophoblast Invasion ◽  
Spiral Artery ◽  
Sectional Study ◽  
Cross Sectional ◽  
In Pregnancy

Preeclampsia is a pregnancy related high blood pressure disorder. It involves defective trophoblast invasion and decreased spiral artery remodelling. Alterations in micronutrients have been identified as one of the risk factor of preeclampsia. In this study we have estimated the levels of zinc, copper, iron and magnesium in preeclampsia and normal pregnant women. Our study revealed a significant decrease of zinc, copper and magnesium levels and significant increase of iron levels in preeclampsia compared to normal pregnant women. Thus assessment of micronutrients in pregnancy helps in decreasing the incidence of preeclampsia. Keywords: Preeclampsia, Zinc, Copper, Iron, Magnesium.

PPARγ controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development

2015 ◽  
Vol 309 (4) ◽  
pp. E357-E369 ◽  
Author(s):  
Vanessa Garnier ◽  
Wael Traboulsi ◽  
Aude Salomon ◽  
Sophie Brouillet ◽  
Thierry Fournier ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Trophoblast Cell ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Placental Development ◽  
Human Trophoblast ◽  
Pparγ Agonist

PPARγ-deficient mice die at E9.5 due to placental abnormalities. The mechanism by which this occurs is unknown. We demonstrated that the new endocrine factor EG-VEGF controls the same processes as those described for PPARγ, suggesting potential regulation of EG-VEGF by PPARγ. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). This study sought to investigate whether EG-VEGF mediates part of PPARγ effects on placental development. Three approaches were used: 1) in vitro, using human primary isolated cytotrophoblasts and the extravillous trophoblast cell line (HTR-8/SVneo); 2) ex vivo, using human placental explants ( n = 46 placentas); and 3) in vivo, using gravid wild-type PPARγ+/− and PPARγ−/− mice. Major processes of placental development that are known to be controlled by PPARγ, such as trophoblast proliferation, migration, and invasion, were assessed in the absence or presence of PROKR1 and PROKR2 antagonists. In both human trophoblast cell and placental explants, we demonstrated that rosiglitazone, a PPARγ agonist, 1) increased EG-VEGF secretion, 2) increased EG-VEGF and its receptors mRNA and protein expression, 3) increased placental vascularization via PROKR1 and PROKR2, and 4) inhibited trophoblast migration and invasion via PROKR2. In the PPARγ−/− mouse placentas, EG-VEGF levels were significantly decreased, supporting an in vivo control of EG-VEGF/PROKRs system during pregnancy. The present data reveal EG-VEGF as a new mediator of PPARγ effects during pregnancy and bring new insights into the fine mechanism of trophoblast invasion.

scholarly journals MON-025 Activin a Increases Human Trophoblast Invasion by Up-Regulating Integrinb1 Through ALK4

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shiqin Zhu ◽  
Peter C Leung ◽  
Jinlong Ma ◽  
Yan Li
Keyword(s):  
Cell Invasion ◽  
Activin A ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Type I ◽  
Trophoblast Cells ◽  
Integrin Β1 ◽  
Down Regulation ◽  
Human Trophoblast

Abstract Activin A Increases Human Trophoblast Invasion by Up-regulating Integrin β1 Through ALK4 Following implantation, extravillous trophoblast cells (EVTs) derived from trophectoderm invade into the maternal decidua to a certain extent, which is tightly regulated by a variety of factors. Activin A, a member of the TGF-β superfamily, has been shown to stimulate the invasion of human trophoblasts (1). Integrin β1 has been implicated in cancer cell invasion and is consistently expressed in human preimplantation embryos (2). However, whether integrin β1 is integrated in activin A signaling and mediates activin A increased-human trophoblast invasion remain unknown. The objective of our study was to investigate the possible mediation role of integrin β1 in the pro-invasive effect of activin A on trophoblasts and illustrate the underlying molecular mechanisms. Primary and immortalized (HTR8/SVneo) cultures of human trophoblast cells were employed as study models. Real-time qPCR, Western blot, and small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions. The integrin β1 protein levels in poorly invasive BeWo,JAR and JEG-3 human choriocarcinoma cells were lower than that in highly invasive HTR8/SVneo cells and primary human EVTs, suggesting the possible essential role of integrin β1 in mediating human trophoblast invasion. The expression levels of integrin β1 were up-regulated in a time-dependent manner after activin A treatment in HTR8/SVneo cells. Importantly, siRNA-mediated down-regulation of integrin β1 significantly attenuated both basal and activin A-induced cell invasion in HTR8/SVneo cells as measured by transwell invasion assay. Interestingly, the TGF-β type I receptors (ALK4/5/7) inhibitor SB431542 abolished activin A-induced activation of SMAD2/SMAD3 as well as activin A-up-regulated integrin 1 expression. Moreover, siRNA-mediated down-regulation of ALK4 or SMAD4 attenuated activin A-up-regulated integrin β1 in both HTR8/SVneo cells and human primary EVT cells. These results reveal that activin A promotes human trophoblast cell invasion by up-regulating integrin β1 expression through ALK4-activated SMAD2/3-SMAD4 signaling pathway. Reference: (1) Bearfield et al., Eur J Endocrinol 2005;152:909–16. (2) Campbell et al., Hum Reprod 1995;10:1571–8.

scholarly journals Tizanidine hydrochloride exhibits a cytotoxic effect on osteosarcoma cells through the PI3K/AKT signaling pathway

2019 ◽  
Vol 47 (8) ◽  
pp. 3792-3802
Author(s):  
Xue-Wu Xing ◽  
Yu-Fu Sun ◽  
Jun Zhao ◽  
Zi-Xiang Pan ◽  
Wen-Xue Jiang
Keyword(s):  
Signaling Pathway ◽  
Adrenergic Receptors ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Expression Levels ◽  
Underlying Mechanisms

Objectives α2-adrenergic receptors are reportedly involved in cancer cell proliferation, invasion, and apoptosis through regulation of diverse molecules, which implies that it contributes to tumor progression. However, the functional significance of α2-adrenergic receptors in osteosarcoma (OS) is unclear. Tizanidine hydrochloride (THC), an α2-adrenergic receptor agonist, is often used to alleviate symptoms of spasticity. This study investigated the functional implications of THC treatment on human OS cells and the underlying mechanisms of resulting changes. Methods The proliferation of U2 OS cells was assessed by Cell Counting Kit-8; the migration and invasion capacities of U2 OS cells were then analyzed by transwell assay. Moreover, apoptosis in U2 OS cells was evaluated by flow cytometry and western blot analyses. Additionally, expression levels of key proteins in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were measured. Results THC inhibited the proliferation, migration, and invasion of U2 OS cells, but promoted apoptosis within these cells. Expression levels of p-AKT, p-mTOR, and p-P70S6K were reduced by exposure to THC, suggesting involvement of PI3K/AKT signaling in THC-induced cytotoxicity within OS cells. Conclusions THC may play a novel role in OS cell cytotoxicity, and these findings suggest a potent therapeutic strategy for OS treatment.

scholarly journals The miR-146b-5p promotes Ewing’s sarcoma cells progression via suppressing the expression of BTG2

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110020
Author(s):  
Lizhen Qu ◽  
Wu Zhang ◽  
Jiajiang Li ◽  
Peng Liu
Keyword(s):  
Cell Lines ◽  
Target Genes ◽  
Es Cells ◽  
Human Mesenchymal Stem Cells ◽  
Migration And Invasion ◽  
Es Cell ◽  
Expression Levels ◽  
Mirna Array ◽  
Underlying Mechanisms ◽  
Sarcoma Cells

Ewing sarcoma (ES) is a malignant tumor that occurs mostly in children. However, the underlying mechanisms of ES are still unknown. Analyzing the results of two previous miRNA array reports, we found that miR-146b-5p might be an onco-miRNA in ES progression. To test this hypothesis, we detected the expression levels of miR-146b-5p by real-time PCR and observed the effects of miR-146b-5p on the progression of ES cells by CCK8 and transwell assays. Bioinformatics and luciferase assays were used to identify the target genes of miR-146b-5p. It showed that the expression levels of miR-146b-5p were upregulated in ES cell lines compared with human mesenchymal stem cells (MSCs). Up- or downregulation of miR-146b-5p in ES cell lines could effectively promote or block the proliferation, migration, and invasion of ES cells, respectively. Furthermore, we demonstrated that BTG2 was one of the target genes and mediated the effects of miR-146b-5p in ES cells. Interestingly, we also found that miR-146b-5p was partly involved in the anticancer effects of pemetrexed in ES cells. Our study revealed that miR-146b-5p affected the progression of ES by suppressing BTG2, which might shed light on anticancer drug development and ES treatment in the future.

scholarly journals Maternal Serum Matrix Metalloproteinase 14 (MMP14) in Early Onset Preeclampsia and Normal Pregnancy

2020 ◽  
Vol 86 ◽  
pp. 01004
Author(s):  
H Sumawan ◽  
Sutrisno
Keyword(s):  
Matrix Metalloproteinases ◽  
Pregnant Women ◽  
Early Onset ◽  
Normal Pregnancy ◽  
Diagnostic Value ◽  
Maternal Serum ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Significant Difference ◽  
Early Onset Preeclampsia

Matrix Metalloproteinases 14 presumably play for cytotrophoblast migration and invasion of the uterine wall and in the remodeling of the spiral arteries in pregnancy. Inadequate trophoblastic invasion leads to an inappropriate vascular remodeling, which generates conditions of hypoxia and increased oxidative stress in the placenta early onset preeclampsia. Therefore, it is particularly important to investigating whether MMP14 altered and can be used as biomarker of preeclampsia. There have been no studies done to measure MMP14 in serum maternal between early onset preeclampsia and normal pregnancy The purpose of this study was to analyse whether maternal serum matrix metalloproteinases 14 levels differ in early onset preeclampsia and uncomplicated pregnancies. This crosssectional study was carried out in 20 subjects with early onset preeclampsia and 20 subjects of normotensive pregnant women range 24 up to 34 weeks of gestation. The study was conducted in Margono Hospital Purwokerto, Indonesia. Level of MMP 14 was measured in maternal serum using an enzyme-linked immunosorbent assay (ELISA). The mean difference was statically analysed by independent samples T-test and ROC curve to determine sensitivity and specificity of MMP 14.Women age, gestational age, parity and body mass index showed a non significant difference between both groups. In this study level MMP 14 in serum was higher in pregnant women with preeclampsia compared to the normotensive ( 266.41 vs 46.80 pg/dl ; p<0.00). Moreover, the area under curve of serum MMP 14 was 0.936, standard error 0.043, p<0.00. The optimal cut-off value of serum MMP at 110.73 pg/dl showed a high diagnostic value in preeclampsia with a sensitivity of 90 % and a specificity of 90%. Maternal serum MMP 14 was higher in preeclampsia and the important finding is the MMP 14 probably become a marker to predict early onset preeclampsia.

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