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

Pingping Peng,Jing Tao,Jingqiong Zhan,Jufang Qin,Huigai Ma,Huamei Song,Dandan Xin,Aihua Chen,Wenfei Zheng,Xiaoqing Yuan,Chenghong Xie

doi:10.1186/s40659-021-00351-5

Pingping Peng, Jing Tao + Show 9 more

Open Access

https://doi.org/10.1186/s40659-021-00351-5

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Abstract

ObjectiveThis study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE).MethodsExpression 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.ResultsCompared 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.ConclusionmiR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

Highlights

Preeclampsia (PE) is a syndrome of pregnancy characterized by hypertension and proteinuria [1], which is a dominant cause of maternal and perinatal deaths withPeng et al Biol Res (2021) 54:30(EMT), are able to establish maternal–fetal linkage [5]
The online software StarBase predicted the binding sites of miR-146a-5p in the 3′UTR of Wnt2, which implied that the interplay of miR-146a-5p and Wnt2 may play a role in regulating trophoblast cell progression
We demonstrated the involvement of miR146a-5p/Wnt2 axis in the trophoblast cell progression and Epithelial-mesenchymal transition (EMT) event, which could provide a latent approach for improving the invasive and migratory capacities of trophoblast cells and mitigating PE development

Summary

Introduction

(EMT), are able to establish maternal–fetal linkage [5] In this regard, insufficient acquisition of invasive and migratory capacities by trophoblast cells plays a vital role in the onset of PE. Dysregulated EMT of trophoblast cells in PE induces defective migration and invasion [5]. These findings emphasize the demand for disclosing the effective regulators of trophoblast cell progression, especially of trophoblast EMT process. As a mature miRNA generated by miR-146a, miR-146a-5p shows suppressive effects on the proliferative, invasive and migratory capacities of breast cancer cells [11] and on the EMT process of oesophageal squamous cells [12]. The online software StarBase predicted the binding sites of miR-146a-5p in the 3′UTR of Wnt, which implied that the interplay of miR-146a-5p and Wnt may play a role in regulating trophoblast cell progression

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Conclusion