miR-101-5p contributes to preeclampsia via modulating the DUSP6- ERK1/2 axis

Background: Preeclampsia (PE) is defined as new-onset hypertension with proteinuria or end-organ dysfunction after 20 weeks of gestation. Defective placentation due to dysregulated behaviors of trophoblast cells is considered a predominant cause of PE. Recently, increasing evidence has suggested an association between microRNAs and PE progression. This study aims to explore the effect of miR-101-5p on trophoblast cell function and the pathogenesis of PE. Methods Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH)-immunofluorescence (IF) double labeling were used to determine miR-101-5p expression levels and localization. Wound-healing, transwell, EdU, and flow cytometry assays were used to examine migration, invasion, proliferation, and apoptosis. Transcriptomics and bioinformatics analysis revealed potential targets and pathways for miR-101-5p. The direct binding between miR-101-5p and DUSP6 was confirmed by Western blotting and the dual-luciferase reporter assay. Expression levels of DUSP6, p-ERK1/2, and ERK1/2 were examined by Western blotting. Results MiR-101-5p was upregulated in preeclamptic placentas when compared with normal controls and was mainly located in various trophoblast cell subtypes. Overexpression of miR-101-5p impaired the migration and invasion of HTR8/SVneo cells but did not affect proliferation or apoptosis. DUSP6 was predicted as a potential downstream target of miR-101-5p. In HTR8/SVneo cells, exogenous transfection of miR-101-5p reduced DUSP6 expression, and miR-101-5p was bound to DUSP6 directly. DUSP6 upregulation rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence of miR-101-5p overexpression. Moreover, miR-101-5p could enhance ERK1/2 phosphorylation by downregulating DUSP6. Conclusions Overexpression of miR-101-5p inhibited the migration and invasion of trophoblast cells by targeting DUSP6 and activating the MAPK/ERK1/2 signaling pathway. Thus, the newly identified miR-101-5p/DUSP6/ERK1/2 axis provides a novel insight into the pathogenesis of PE.