Roles of noncoding RNAs in preeclampsia

Sun, Ningxia; Qin, Shiting; Zhang, Lu; Liu, Shiguo

doi:10.1186/s12958-021-00783-4

Reproductive Biology and Endocrinology

Table 1 Dysregulation of miRNAs in PE

From: Roles of noncoding RNAs in preeclampsia

MiRNA	Sample type	Status	Targets	Function	Ref.
miR-210	Serum/placenta	upregulated	NOTCH1/PTPN2/THSD7A/KCMF1/FOXA1	Upregulation of miR-210 decreased NOTCH1/PTPN2/THSD7A/KCMF1 expression, impaired HTR-8/SVneo proliferation, migration, invasion, and tube-like formation capabilities, and promoted apoptosis.	[18,19,20,21,22,23]
miR-182-5p	placenta	upregulated	RND3	the increased miRNA-182-5p expression could inhibit the migratory and invasive ability of trophoblast cells through targeted degrading RND3 protein	[24]
miR-155	placenta/placenta-associated serum exosomes	upregulated	CYR61/Cyclin D1	Overexpression of miR-155 in HTR-8/SVneo cells inhibited cell invasion, proliferation and increased cell number at the G1 stage in trophoblast cells	[16, 25]
miR-155-5p	placenta	upregulated	eNOS	miR-155 inhibited cell invasion in trophoblast cells, and the effect was rescued by over expression of eNOS.	[26]
miR-195	placenta	downregulated	ActRIIB/ActRIIA	miR-195 could promote cell invasion via directly targeting ActRIIB/ActRIIA in human trophoblast cells	[27]
miR-16	placenta/mesenchymal stem cell (MSC)	upregulated	CCNE1 /VEGF-A/Notch2	over-expressed miR-16 inhibited the proliferation and migration of decidua-derived mesenchymal stem cells /BeWo and JEG-3 cells, and induced cell-cycle arrest by targeting cyclin E1	[28, 29]
miRNA-376c	placenta/plasma/exosome	downregulated	ALK5/ALK7/25-OH-VD	miR-376c inhibits both ALK5 and ALK7 expression to impair transforming growth factor-β/Nodal signaling, leading to increases in cell proliferation and invasion	[30, 31]
miR-29b	decidua-derived mesenchymal stem cell (dMSC)/placenta	upregulated	MMP2/MCL1/ VEGFA/ ITGB1/HDAC4	miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells.	[32]
miR-101	placenta	downregulated	ERp44/BRD4/CXCL6	miR-101 could promote apoptosis and inhibite the proliferation and migration of trophoblasts	[10, 33, 34]
miR-18a	placenta/plasma	downregulated	Smad2/ER1/ESRα	miR-18a could promote trophoblast cell invasion and suppress apoptosis of human trophoblast cells	[35,36,37]
miR-20a	placenta	upregulated	Foxa1/VEGF	the upregulated miR-20a in human preeclampsia tissue can inhibit the proliferative and invasive activities of trophoblast cells	[23, 38]
miR-125b-1-3p	placenta	upregulated	S1PR1	miR-125b-1-3p inhibited the invasiveness of human trophoblast cells,	[39]
miR-125b	placenta/plasma	upregulated	SGPL1/ STAT3/KCNA1 /GPC1/Trop-2	upregulated miR-125b can impair endothelial cell function, reduce cell proliferation and invasion and migration	[40,41,42,43]
miR-126	placenta	downregulated	VEGF/ PIK3R2	miR-126 enhanced endothelial progenitor cell (EPC) proliferation, differentiation and migration	[44, 45]
miR-196b	plasma	downregulated	/	/	[46]
miR-206	plasma	upregulated	VEGF/IGF-1/ET-1	miR-206 modulated trophoblast cells migration and invasion	[47,48,49]
miR-494	Mesenchymal stem cells(MSC)/serum exosomes	upregulated	VEGF/CDK6	supernatant from miR-494-overexpressing dMSCs could reduce HTR-8/SVneo migration, impair HUVEC capillary formation and arrest G1/S transition	[50, 51]
miR-519d-3p	placenta	upregulated	MMP-2	upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2	[52]
miR-335	placenta	upregulated	eNOS/Sp1	miR-335-5p could inhibit transforming from epithelial to mesenchymal and cell migration	[53, 54]
miR-584	placenta	upregulated	eNOS	miR-335 inhibited the migratory ability of the trophoblast cells, and the effect was ‘rescued’ by overexpressed eNOS	[53]
miR-34a	placenta	upregulated	MYC/BCL-2, Notch-1	Overexpression of miR-34a inhibited cell proliferation, migration and invasion, and induced trophoblast cell apoptosis by inhibiting expression of BCL-2 protein	[55,56,57]
miR-204	placenta	upregulated	MMP-9	miR-204 may contribute to the development of preeclampsia by inhibiting trophoblastic invasion	[58]
miR-193b-3p	placenta	upregulated	TGF-β2	miR-193b-3p could regulate trophoblasts migration and invasion through binding onto the 3’UTR target site of TGF-β2	[59]
miR-193b-5p	placenta	upregulated	APLN/FGF13	Overexpression of miR-193b-5p inhibited trophoblast cell proliferation and migration	[60]
miR-203	placenta	upregulated	VEGFA/SOCS-3	miR-203 overexpression inhibited the proliferation, migration and invasion ability of HTR-8/SVneo cells, meanwhile which increased the endothelial inflammatory response	[61,62,63]
miRNA-203a-3p	placental mononuclear cells and exosomes	downregulated	IL24	microRNA-203a-3p was able to suppress the proliferation capacity of LPS-stimulated mononuclear macrophages, and it exerted anti-inflammatory effects via down-regulating IL24 in THP-1 cells.	[64]
miR-885-5p	placenta	upregulated	MMP-9	/	[65]
miR-141	placenta/plasma	upregulated	EG-VEGF/ CXCL12β/ CXCR2 / 4	miR-141 could inhibit the invasion and vascularization abilities, and promote the apoptosis of HTR-8/SVneo cells	[66, 67]
miR-141-5p	placenta	downregulated	ATF2	miR-141-5p up-regulated transcription factor ATF2 to promote phosphatase DUSP1 expression, which reduces p-MAPK1 and ERK1/2 expression to promote 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	miR-93 reduced migration and invasion of immortalized trophoblast cells.	[78]
miR-144	placenta	downregulated	PTEN	miR-144 induced significant increase in cell proliferation, migration, invasion, and decrease in cell apoptosis, and also affected the cell cycles	[79]
miR-144-3p	placenta	downregulated	Cox-2	Downregulation of miR-144-3p led to systemic inflammation and endothelial cell injury	[80]
miR-942	plasma	downregulated	ENG	Decreased miR-942 expression decreased the invasive ability of TEV-1 cells, and inhibited the HUVEC angiogenesis assay	[81]
miR-134	placenta	upregulated	ITGB1	MiR-134 suppressed the infiltration of trophoblast cells by targeting ITGB1	[82]
miR-362-3p	placenta	upregulated	Pax3	miR-362-3p/Pax3 axis regulates cell viability, migration and invasion of HTR8/SVneo cells under hypoxia.	[83]
miR-454	placenta	downregulated	EPHB4/ALK7	MiR-454 promotes the proliferation and invasion of trophoblast cells, and inhibit the apoptosis	[84, 85]
miR-30a-3p	placenta	upregulated	IGF-1	the over-expression of miR-30a-3p alter the invasive capacity of JEG-3 cells and induce the apoptosis of HTR-8/SVneo cells	[86]
miR-31-5p	serum	upregulated	eNOS	NF-κB-responsive miR-31-5p elicits endothelial dysfunction, hypertension, and vascular remodeling via post-transcriptional down-regulation of eNOS	[87]
miR-423–5p	plasma	upregulated	IGF2BP1	MiR-423-5p inhibited migration, invasion and proliferation as well as induced apoptosis in HTR-8/SVneo cells.	[88]
miR-299	placenta	upregulated	HDAC2	miR-299 suppressed the invasion and migration of trophoblast cells partly via targeting HDAC2	[89]
miR-4421	placenta	upregulated	CYP11B2	overexpression of miR-4421 inhibited trophoblast proliferation and significantly blocked cell cycle	[90]
miR-320a	placenta	upregulated	IL-4/ERRγ	Excessive miR-320a expression remarkably suppressed trophoblast invasion and proliferation	[12, 91]
miR-517-5p	placenta	upregulated	MMP-2	MiR-517-5p could promote proliferative and invasive abilities of JAR cells by inhibiting ERK/MMP-2 pathway	[92]
miR-517c-3p	plasma	upregulated	TNFSF15	miR-517c-3p could suppress cell growth and proliferation, and promote placental hypoxia, immune response and apoptosis.	[93]
miR-let-7d	placenta	upregulated	/	low expression levels of miR-let-7d plays a central role in suppressing apoptosis in addition to promoting the proliferation and invasion of PE TCs.	[94]
miR-218-5p	placenta	downregulated	TGF-β2	miR-218-5p accelerated spiral artery remodeling in a decidua-placenta co-culture and promoted trophoblast invasion and enEVT differentiation	[95]
miR-181a-5p	placenta	upregulated	IGF2BP2	miR-181a-5p may trigger antiproliferation and inhibition of cell cycle progression, induce apoptosis, and suppress invasion in HTR-8/SVneo and JAR cells	[96]
miR-142-3p	placenta	upregulated	TGF-β1	miR-142-3p suppressed cell invasion and migration by reactivating the TGF-β1/Smad3 signaling pathway.	[97]
miR-145-5p	placenta	downregulated	FLT1/Cyr61	miR-145-5p promoted trophoblast cell growth and invasion	[98, 99]
miR-30b	placenta	upregulated	MXRA5	miR-30b might contribute to PE through inhibiting cell viability, invasion while inducing apoptosis of placental trophoblast cells via MAPK pathway by targeting MXRA5.	[100]
miR-454	placenta	downregulated	ALK7/EPHB4	miR-454 promotes the proliferation and invasion of trophoblast cells by inhibiting EPHB4 /ALK7	[84, 85]
miR-200a	plasma	upregulated	EG-VEGF/TTR	miR-200a suppressed primary cilia formation and inhibited trophoblast invasion.	[101, 102]
miR-548c-5p	placenta/ serum exosome	downregulated	PTPRO	miR-548c-5p could inhibit the proliferation and activation of LPS-stimulated macrophages and decrease levels of inflammatory cytokines	[103]
miR-342-3p	placenta	upregulated	PDGFRA/ID4	miR-342-3p was proposed to inhibit the proliferation, migration, invasion and G1/S phase transition of HTR8/SVneo cells	[104, 105]
miR-431	placenta	upregulated	ZEB1	miR-431 inhibited the migration and invasion of trophoblastic cells	[106]
miR-221-3p	placenta	downregulated	THBS2	miR-221-3p overexpression inhibited apoptosis, increased cell population at S phase, and decreased cell population at G0/G1 phase of HTR-8/SVneo cells	[107]
miR-152	placenta	upregulated	VEGF	the increased miR-152 expression can promote the apoptosis of trophoblast cells.	[108]
miR-133	serum	upregulated	Rho/ROCK	MiR-133 may affect the apoptosis of trophoblasts in the placenta tissues	[109]
miR-384	placenta/plasma	upregulated	PTBP3	Cell proliferation and migration were inhibited by miR-384 overexpression	[110]
miR-21	Serum/placenta	upregulated	FOXM1	MiR-21 may regulate placental cell proliferation	[111]
miR-125a-5p	placenta/exosome	upregulated	VEGFA	miR-125a-5p might affect HTR8/SVneo cell proliferation and migration and inhibit angiogenesis	[112]
miR-214-3p	serum	upregulated	PIGF	Downregulation of miR-214-3p promoted trophoblast invasion into the decidua, as well as spiral artery remodeling	[113]
miR-518b	plasma	upregulated	EGR1	Increased miR-518b inhibited trophoblast migration and angiogenesis	[114]
miRNA-646	serum	upregulated	VEGF-A	miR-646 suppressed endothelial progenitor cells (EPCs) multiplication, differentiation and migration.	[115]
miR-215-5p	placenta	upregulated	CDC6	miR-215-5p inhibited both the migration and invasive potential of trophoblasts, besides decreasing the G1-S transition in HTR-8/SVneo cells	[116]
miR-483	venous blood/ umbilical cord blood / placental tissue	downregulate	IGF1	miR-483 regulates the expression of PI3K, Akt, and mTOR in endothelial progenitor cells	[117]

Back to article page

ISSN: 1477-7827

Contact us

General enquiries: journalsubmissions@springernature.com