Open AccessMicroRNA‑142‑3p inhibits trophoblast cell migration and invasion by disrupting the TGF‑β1/Smad3 signaling pathway
Author(s) -
Enling Liu,
Zheng Liu,
Yifeng Zhou,
Mei Chen,
Liqun Wang,
Jun Li
Publication year - 2019
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2019.9997
Subject(s) - trophoblast , biology , gene knockdown , microrna , mmp2 , cell migration , microbiology and biotechnology , cancer research , microarray analysis techniques , oncogene , cell growth , mmp9 , signal transduction , cell , cell cycle , placenta , downregulation and upregulation , gene expression , apoptosis , gene , genetics , pregnancy , fetus
Insufficient invasion of trophoblasts is known to be associated with preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been reported to serve important roles in the pathogenesis of PE. However, little is known regarding the regulation of trophoblastic invasion by miRNAs. The aim of the present study was to explore the role of miRNAs in trophoblastic invasion and the underlying molecular mechanism. Using a miRNA microarray, miRNAs putatively involved in the pathophysiology of PE were examined between normal and preeclamptic placentas. Validation analysis of miR‑142‑3p level in placenta specimens was performed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Then, the regulation of miR‑142‑3p on trophoblast cells migration and invasion was evaluated using wound healing and transwell migration assays. Furthermore, the target gene of miR‑142‑3p and the downstream signaling pathway were also investigated. Microarray analysis and RT‑qPCR revealed that miR‑142‑3p was significantly upregulated in placenta specimens from patients with PE. Its overexpression inhibited trophoblast cell invasion and migration, whereas its knockdown enhanced trophoblast cell invasion and migration. In addition, overexpression of miR‑142‑3p inhibited the mRNA expression and the activities of matrix metalloproteinase‑2 (MMP2) and MMP9, which are closely associated with cell invasion and migration, while inhibition of miR‑142‑3p had the opposite result. Subsequent analyses demonstrated that transforming growth factor‑β1 (TGF‑β1) was a direct and functional target of miR‑142‑3p. Notably, the knockdown of TGF‑β1 effectively reversed the enhancement of miR‑142‑3p inhibitor on trophoblast cell invasion and migration. Finally, the present study confirmed that miR‑142‑3p inhibitor enhanced cell invasion and migration by reactivating the TGF‑β1/Smad3 signaling pathway. Taken together, the results of the present study suggest that miR‑142‑3p may serve an important role in human placental development by suppressing trophoblast cell invasion and migration through disruption of the TGF‑β1/smad3 signaling pathway, suggesting that knockdown of miR‑142‑3p may provide a novel therapy for PE.