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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]