MicroRNA-20b inhibits trophoblast cell migration and invasion by targeting MMP-2

Meiyuan Jin; Haiyang Li; Hongfeng Xu; Gaoxiang Huo; Yingyu Yao

MicroRNA-20b inhibits trophoblast cell migration and invasion by targeting MMP-2

Int J Clin Exp Pathol. 2017 Nov 1;10(11):10901-10909. eCollection 2017.

Authors

Meiyuan Jin¹, Haiyang Li², Hongfeng Xu³, Gaoxiang Huo⁴, Yingyu Yao¹

Affiliations

¹ Department of Obstetrics, Tongde Hospital of Zhejiang Province Hangzhou, China.
² Department of Gynaecology and Obstetrics, Zhoushan Municipal Women and Children Health Care Center Zhoushan, China.
³ Department of Gynaecology and Obstetrics, Cixi Municipal Women and Children Health Care Center Cixi, China.
⁴ Department of Obstetrics, The People's Hospital of Cangzhou City Cangzhou, China.

PMID: 31966433
PMCID: PMC6965854

Abstract

Insufficient trophoblast migration/invasion is associated with the preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been confirmed to be involved in the pathogenesis of PE. The aim of the present study was to evaluate whether miRNAs is involved in the procession of PE by regulating the migration/invasion of trophoblast. First, we compared the expression profiles of miRNAs between normal and preeclamptic placentas using microarray. Validation analysis of miR-20b level in placentas and peripheral blood specimens was performed using quantitative reverse transcription PCR (qRT-PCR). Then, the effects of miR-20b on trophoblast cell migration and invasion were evaluated using wound healing assay and transwell migration assay. Further bioinformatics analysis, luciferase reporter assays and Western blot were performed to identify its target genes. The correlation between miR-20b and matrix metalloproteinase-2 (MMP-2) in placentas was determined by Pearson's correlation coefficient. Finally, HTR8/SVneo cells were co-transfected with miR-20b inhibitor and si-MMP-2 to explore the molecular mechanism by which miR-20b functions in the trophoblast migration/invasion. We found that miR-20b was elevated in placentas and peripheral blood specimens from preeclampsia patients. Further results show that overexpression of miR-20b significantly inhibited the invasiveness of human trophoblast cells, whereas miR-20b knockdown enhanced trophoblast cell invasion. Matrix metalloproteinase-2 (MMP-2), the most common enzymes in remodeling extracellular matrix components for metastasis, was proved to be a direct target of miR-20b. Inhibition of MMP-2 by siRNA could reverse the promoting effect of miR-20b inhibition on the invasion of trophoblast cells. Taken together, our study indicates that miR-20b inhibited trophoblastic invasion by targeting MMP2. The miR-20b/MMP-2 axis may provide novel insights into understanding the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for PE.

Keywords: HTR8/Svneo; matrix metalloproteinase 2; microRNA-20b; pre-eclampsia; trophoblast invasion.