MicroRNA-155 inhibits migration of trophoblast cells and contributes to the pathogenesis of severe preeclampsia by regulating endothelial nitric oxide synthase

Abstract

The aim of the present study was to characterize the role of microRNA (miR)-155 in the pathogenesis of severe preeclampsia (PE). A total of 19 severe preeclampsic and 22 normal placentas were collected to measure miR-155 and endothelial nitric oxide synthase (eNOS) expression using quantitative (q)PCR and western blot analysis. The results demonstrated a significant increase in the levels of miR-155 and decreased eNOS expression in the severe preeclampsic placentas, as compared with the normal controls. In order to examine the function of miR-155 in the human placenta, the HTR8/Svneo cell line was transiently transfected with an miR-155 mimic or its inhibitor, anti-miR-155. It was confirmed that miR-155 may suppress the expression of eNOS in HTR-8/SVneo cells. Furthermore, a transwell insert invasion assay demonstrated that miR-155 inhibited cell invasion in trophoblast cells, and the effect was rescued by over expression of eNOS. The present study revealed that miR-155 has a negative regulatory role in the migratory behavior of HTR-8/SVneo cells via modulating eNOS.

miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia

“…Some miRNAs are reported to be deregulated in the placenta of preeclampsia, further studies revealed that they were related to angiogenesis, inflammation and trophoblast cell migration/invasion [20,[22][23][24][25][26][27][28][29]. Thus far, it remains to be clarified that how the deregulated miRNAs involve in the development of preeclampsia.…”

“…Several previously studies found about 600 miRNAs expressed in human placenta and profiled genomewide expression of miRNAs in normal and preeclamptic placentas [13][14][15][16][17][18][19]. Although little is known about what roles of miRNAs play in human placenta development and functions, recent reports suggested that preeclampsia-associated aberrant expressed miRNAs play critical roles in human placentas development and function via regulating specific genes with various cell functions [20][21][22][23][24][25][26][27][28][29].…”

Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

“…For example, overexpression of miR-378a-5p and miR-376c enhanced these processes [77, 78]. So far, only a handful of miRNAs, including miR-424 [79], miR-101 [52], miR-18a [46], miR-335 [50], miR-137 [55], and miR-155 [61], have been implicated in trophoblast dysfunction through various targets, including endothelial nitric oxide synthase (eNOS) and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1 or sFlt-1).…”

“…In addition, miR-155 was linked to the trophoblast function, including proliferation, invasion, and differentiation [59, 60]. Recently, miR-155 was shown to modulate eNOS expression in trophoblast cells [61]. Another highly studied miRNA, miR-210, was first identified in trophoblast cells as an iron metabolism regulator responding to hypoxia stress and implicated in the defective placentation [71].…”

The role of microRNAs in the proliferation, differentiation, invasion, and apoptosis of trophoblasts during the occurrence of preeclampsia—A systematic review

“…Another miRNA that is consistently overexpressed in preeclampsia is miR-155 [32,42,69,72] and studies have indicated that miR-155 is important to the regulation of trophoblast invasion [72,86]. miR-155, a common target of a large range of inflammatory mediators, is able to be upregulated by a range of inflammatory factors including interferon b, lipopolysaccharide, TNF-a, and IL-1b; this occurs via the TLR [87].…”