MiR‐95‐5p involves in the migration and invasion of trophoblast cells by targeting low density lipoprotein receptor‐related protein 6

Abstract

AimsLow density lipoprotein receptor‐related protein 6 (LRP6) has been demonstrated to control trophoblast cell invasion, but its regulatory gene remains undefined. In this study, microRNA (miR) regulating LRP6 were explored to elucidate the potential mechanism of preeclampsia (PE).MethodsFirstly, the expression of LRP6 in PE tissues was detected by immunohistochemical staining and quantitative real‐time polymerase chain reaction (qRT‐PCR) assay. Prediction software predicted that LRP6 might be the target gene of miR‐95‐5p, and verified by double‐luciferase reporter analysis. qRT‐PCR assay measured the expression of miR‐95‐5p in PE tissues and trophoblast cell lines. Then, we transfected miR‐95‐5p mimic, inhibitor, LRP6, or mimic plus LRP6 into trophoblast cell lines, and analyzed their influences on cell migration and invasion by wound healing and Transwell experiments. The expressions of matrix metalloproteinase (MMP)‐2, MMP‐9 and tissue inhibitors of metalloproteinase (TIMP)‐1 in transfected cells were examined by western blot (WB) analysis.ResultsLRP6 was low‐expressed in PE tissues, while miR‐95‐5p expression was high‐expressed. MiR‐95‐5p negatively regulated the LRP6 expression in trophoblast cells. Both up‐regulated LRP6 and down‐regulated miR‐95‐5p can not only promote the migration and invasion of trophoblast cells, but also raised the expressions of MMP‐2 and MMP‐9 and inhibited the expression of TIMP‐1. The over‐expression of miR‐95‐5p suppressed the metastasis of trophoblast cells and rescued LRP6‐induced increase of MMP‐2 and MMP‐9 and reduction of TIMP‐1.ConclusionMiR‐95‐5p involved in the migration and invasion of trophoblast cells by targeting LRP6, which might be a potential therapeutic target for PE.

MicroRNA-513c-5p is involved in the pathogenesis of preeclampsia by regulating of low-density lipoprotein receptor-associated protein 6

“…Low LRP6 expression might be responsible for lower trophoblast migration and invasion and subsequent PE, and the mechanisms showed a strong association with Wnt/β-catenin pathway [ 26 ]. The overexpression of miR-95-5p regulates the expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in trophoblast cells by targeting LRP6, thereby participating in the metastasis of trophoblast cells and causing the occurrence and progression of PE [ 27 ]. LRP6 was reported to be involved in the proliferation, migration and invasion of trophoblast cells via miR-346 [ 28 ].…”

Role of microRNAs regulating trophoblast cell function in the pathogenesis of pre‑eclampsia (Review)

“…The lncRNA SNHG5 affects expression of miRs by adsorbing miRs and upregulating the transcription of the secreted protein acidic and cysteine-rich gene, thereby inhibiting autophagy in trophoblasts of patients with PE (46). miRs that have been reported to regulate trophoblasts are listed in Table Ⅰ (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58).…”