Aberrantly up-regulated miR-142-3p inhibited the proliferation and invasion of trophoblast cells by regulating FOXM1

Abstract Recurrent miscarriage (RM) is a common reproductive endocrine disease in women of childbearing age. At present, the etiology of RM in approximately 50% women remains unknown. The purpose of this study was to explore the possible mechanism(s) of enolase 1 (ENO1) in RM and to seek a new target for clinical diagnosis and treatment of the disease. In this study, we detected the expression difference of ENO1 in villous tissues between the RM group and the control group, and we found that ENO1 was significantly lower in the RM group. Immunohistochemistry was also performed to examine the localization and expression of ENO1 in villous cytotrophoblast cells, and we found that ENO1 was mainly expressed in the cytoplasm, cell membrane, and nucleus of trophoblast cells. The villous trophoblast cell membrane coloration in the control group was significantly darker than that in the RM group, suggesting that ENO1 is expressed at low levels on the cell membrane of trophoblast cells of RM. ENO1 knockdown significantly inhibited cell migration and proliferation compared with the blank control group. Therefore, we conclude that ENO1 may mediate the occurrence of RM by downregulating the proliferation and invasion of villous trophoblasts. The specific mechanism needs further clarification.

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Suppression of bromodomain-containing protein 4 protects trophoblast cells from oxidative stress injury by enhancing Nrf2 activation

Human & Experimental Toxicology ◽

10.1177/0960327120968857 ◽

2020 ◽

pp. 096032712096885

Author(s):

Yiqing Wu ◽

Yang Mi ◽

Fan Zhang ◽

Yimin Cheng ◽

Xiaoling Wu

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Cell Types ◽

Protective Effects ◽

Trophoblast Cells ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Nrf2 Activation ◽

Brd4 Inhibition ◽

Proliferation And Invasion

Oxidative stress is considered a key hallmark of preeclampsia, which causes the dysregulation of trophoblast cells, and it contributes to the pathogenesis of preeclampsia. Emerging evidence has suggested bromodomain-containing protein 4 (BRD4) as a key regulator of oxidative stress in multiple cell types. However, whether BRD4 participates in regulating oxidative stress in trophoblast cells remains undetermined. The current study was designed to explore the potential function of BRD4 in the regulation of oxidative stress in trophoblast cells. Our data revealed that BRD4 expression was elevated in trophoblast cells stimulated with hydrogen peroxide. Exposure to hydrogen peroxide caused marked decreases in the levels of proliferation and invasion but promoted apoptosis and the production of ROS in trophoblast cells. Knockdown of BRD4, or treatment with a BRD4 inhibitor, markedly increased the levels of cell proliferation and invasion and decreased apoptosis and ROS production following the hydrogen peroxide challenge. Further data indicated that suppression of BRD4 markedly decreased the expression levels of Keap1, but increased the nuclear expression of Nrf2 and enhanced Nrf2-mediated transcriptional activity. BRD4 inhibition-mediated protective effects were markedly reversed by Keap1 overexpression or Nrf2 inhibition. Overall, these results demonstrated that BRD4 inhibition attenuated hydrogen peroxide-induced oxidative stress injury in trophoblast cells by enhancing Nrf2 activation via the downregulation of Keap1. Our study highlights the potential importance of the BRD4/Keap1/Nrf2 axis in the modulation of the oxidative stress response in trophoblast cells. Targeted inhibition of BRD4 may offer new opportunities for the development of innovative therapeutic approaches to treat preeclampsia.

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