Exploration of the regulation and control mechanisms of miR‑145 in trophoblast cell proliferation and invasion

Abstract

Preeclampsia (PE) is the leading cause of maternal and fetal mortality and morbidity. Furthermore, recent studies have reported that miR-145 within the preeclamptic trophoblast debris may cause the high blood pressure via interacting with the maternal endothelium. The aim of the present study was to investigate the functions of miR-145 in PE. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess the expression of miR-145 and mucin (MUC1), respectively. TargetScan, miRBase and miRWalk were used to predict the targets of miR-145. Constructed miR-145 mimic plasmids were transfected into HTR-8/SVneo cells for further experiments, including an MTT assay for cell proliferation, Transwell assay for cell invasion and flow cytometry for cell apoptosis analysis. Additionally, the luciferase reporter gene system was employed for target verification. The results demonstrated that miR-145 is downregulated and MUC1 is upregulated in PE tissues and cells compared with normal placenta tissues and cells. The correlation analysis suggests that the expression of miR-145 is negatively correlated with MUC1. Meanwhile, increased proliferation, enhanced invasion and decreased apoptosis of HTR-8/SVneo cells was observed in miR-145 mimic groups compared with mimic control group. Also, the decreased luciferase activity in the miR-145 mimic group indicates that MUC1 may be a target of miR-145. In summary, the results of the present study suggest that miR-145 may serve key roles in the regulation of trophoblast cell proliferation and invasion by targeting MUC1.

Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis

“…Therefore, miR-145 might influence cellular invasive behaviour not only in cell-type but also invasive/migratory-mode manner and ECM-substrate-dependent manner. While the majority of oncological studies on miR-145 function suggest that it reduces invasive growth by targeting a variety of mRNAs, two studies in trophoblast cells have described invasion-promoting functions of miR-145, which were attributed to a targeting of mucin 1 (MUC1) and leukemia inhibitory factor receptor (LIFR), respectively 59 , 60 . We can only speculate that the 3D spheroid culture compared to 2D culture of 12Z cells may have altered the expression patterns of miR-145 target mRNAs in a way that alters the response to this epigenetic regulator.…”

Roles of noncoding RNAs in preeclampsia

“… [ 68 ] miR-128a placenta upregulated Bax miR-128a induced the apoptosis of HTR-8/SVneo cells by down-regulating Bax through the mitochondrial apoptosis pathway. [ 69 ] miR-145 placenta downregulated PI3K/MUC1 miR-145 may serve key roles in the regulation of trophoblast cell proliferation and invasion [ 70 ] miR-136 Mesenchymal stem cells (MSCs)/serum exosomes upregulated BCL2/VEGF MiR-136 significantly increase the apoptosis and suppress the proliferation of MSCs, and it could also inhibit the capillary formation and trophoblast cell invasion. [ 71 ] miR-520 g serum upregulated MMP-2 Elevated maternal serum level of miR-520 g level in first trimester could suppress the migration and invasion of trophoblast, and might play a role in the defective spiral artery remodeling, [ 72 ] miR-20b placentas and peripheral blood upregulated MMP-2 miR-20b inhibited trophoblastic invasion by targeting MMP2 [ 73 ] miR-23a placenta upregulated XIAP/HDAC2 miR-23a reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis [ 74 , 75 ] miR-495 peripheral blood exosomes/umbilical cord mesenchymal stem cells (UCMSCs) upregulated Bmi-1 The supernatants from miR-495-overexpressed inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC [ 76 ] miR-137 placenta upregulated ERRa MiRNA-137 significantly reduced the proliferation and migration of placenta trophoblast cells [ 77 ] miR-93 placenta/plasma upregulated MMP-2 mi...…”