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Table 4 Dysregulation of lncRNAs in PE

From: Roles of noncoding RNAs in preeclampsia

LncRNA Sample type Status Targets Function Ref.
BC030099 the whole blood (WB) upregulated / / [137]
LOC391533 placenta upregulated sFlt-1 This protein plays an important role in angiogenesis and vasculogenesis. [138]
LOC284100 placenta upregulated / /
CEACAMP8 placenta upregulated / /
HOTAIR placenta upregulated miR-106a High level of HOTAIR represses the proliferation, migration and invasion of trophoblast cells through downregulating miR-106 in an EZH2-dependent manner. [139]
downregulated PUM1/HOTAIR HOTAIR promotes trophoblast invasion by activating PI3K-AKT signaling pathway. [140]
AGAP2-AS1 placenta downregulated JDP2 AGAP2-AS1 knockdown could inhibit trophoblasts proliferation, invasion and spiral artery remodeling and promote cell apoptosis. [141]
HOXA11-AS placenta downregulated miR-15b-5p/HOXA-7/Lsd1 and Ezh2/RND3 Down-regulated HOXA11-AS inhibits trophoblast cell proliferation, migration and invasion, and promoted cell accumulation in G0–G1 phase and apoptosis. [142]
TUG1 placenta downregulated miR-29b/MCL1/VEGFA /MMP2 TUG1 could act as a molecular sponge for miR-29b, thus down-regulating MCL1, VEGFA, and MMP2 to promote cell proliferation, invasion, and angiogenesis, while negatively regulated cell apoptosis. [14]
Ezh2/RND3 Down-regulated TUG1 inhibits trophoblast cell proliferation, migration, invasion and the formation of capillary-like networks and promotes trophoblast cell apoptosis. [143]
miR-204-5p Down-regulated TUG1 negatively regulates trophoblast migration and invasion partly through sponging miR-204-5p and negatively regulating the expression and function of miR-204-5p. [144]
SPRY4-IT1 placenta upregulated Bax/Bcl-2 SPRY4-IT1 overexpression significantly decreases the cell migration, proliferation and spiral artery remodeling, while increases cell apoptosis. [145]
Wnt/β-catenin pathway Overexpression of SPRY4-IT1 suppresses trophoblast cell migration, invasion and spiral artery remodeling by inducing E-cadherin and β-catenin expression and decreasing vimentin expression. [146]
MEG3 placenta downregulated TGF-β/ /E-cadherin/N-cadherin Down-regulated MEG3 induces E-cadherin upregulation and N-cadherin and slug downregulation in HTR-8/SVneo cells, which inhibits trophoblast cell proliferation, migration, invasion and EMT. [147]
Notch1 Down-regulation of MEG3 could downregulate Notch1 expression to suppress trophoblast cells migration, invasion and promote its apoptosis. [148]
NF-κB/Caspase-3/ Bax Down-regulation of MEG3 increases apoptosis and decreases migration of trophoblast cells by influencing expression of NF-κB, Caspase-3, and Bax protein expressions. [149]
H19 placenta downregulated NOMO1/miR-675 Lowered expression of H19 participate in the excessive proliferation of trophoblast cells by downregulating miR-675 which targets NOMO1 and interferes with Nodal signaling. [150]
miR-148a-5p/P28/miR-216-3p/EBI3 Down-regulated could up-regulate the expression of miR-148-5p/miR-216-3p and the expressions of subunits of IL-27, P28 and EBI3 were thus suppressed. [151]
miRNAlet-7/the type III TGF-β receptor (TβR3) H19 repression decreases TGF-β signaling via the Par6/Smurf1/RhoA pathway activated by TβR3, leading to impaired migration and invasion of EVT cells. [152]
upregulated PI3K/AKT/mTOR pathways LncRNA-H19 overexpression reduces cell viability but increases invasion and autophagy in trophoblast cells by enhancing phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathways. [153]
MIR503HG placenta upregulated the matrix metalloproteinase-2/− 9, the snail /E-cadherin/ NF-κB signaling pathway MIR503HG overexpression suppresses cell proliferation, invasion, and migration, and induces apoptosis and causes cell cycle arrest at the G0/G1 phase of HTR-8/SVneo [154]
DLX6-AS1 placenta tissues upregulated miR-149–5p/ERP44 pathway DLX6-AS1 inhibits proliferation and invasion of trophoblast cells, and suppresses angiogenesis of HUVEC cells by binding miR-149–5p/ERP44 pathway. [11]
miR-376c/ GADD45A DLX6-AS1 may contribute to preeclampsia by impairing proliferative, migratory and invasive abilities of trophoblasts via the miR-376c/GADD45A axis. [155]
ZEB2-AS1 placenta downregulated miR-149 / PGF ZEB2-AS1 contributes to PE progression by inhibiting cell proliferative, migratory, invasive capacities and EMT via the miR-149/PGF axis in HTR-8/SVneo cells. [156]
PRNCR1 placenta upregulated MAPK Overexpression of LncRNA PRNCR1 in PE patients reduces the viability of cells, and is positively correlated with systolic blood pressure, diastolic blood pressure and urine protein [157]
GHET1 placenta downregulated the E-cadherin / vimentin /fibronectin GHET1 promotes PE by inhibiting cell proliferative, migratory, invasive capacities and EMT by stimulating E-cadherin and suppressing vimentin and fibronectin. [158]
TDRG1 placenta downregulated miR-214-5p/Notch signaling pathway TDRG1 inhibits cell viability, proliferation, migration, and invasion by stimulating the expression of miR-214-5p and regulating the Notch signaling pathway in trophoblast cells. [159]
MALAT1 placenta downregulated pro-apoptotic proteins Silencing of MALAT-1 in JEG-3 cells suppresses proliferation, migration and invasion, and induces cell cycle arrest at G0/G1 phase and enhancing apoptosis. [160]
N-cadherin/vimentin /E-cadherin/Hu-antigen R (HuR) /FOS Down-regulated MALAT1 inhibits trophoblast invasion, migration, epithelial mesenchymal transition (EMT) and spiral artery remodeling by upregulating E-cadherin and downregulating FOS, N-cadherin, and vimentin. [161]
miR-206/IGF-1 axis Down-regulated MALAT1 regulates miR-206/IGF-1 axis and thereby inhibits trophoblast cells migration and invasion through PI3K/Akt signal pathway. [49]
TCL6 placenta upregulated PTEN/CDK2 Overexpression of lncRNA TCL6 is positively correlated with systolic blood pressure, diastolic blood pressure and urine protein, whereas negatively correlated with fetal birth weight of PE patients [162]
uc003fir placenta /preeclamptic placenta vessels/ vessel-free tissue upregulated CCL5/miR-155 Over-expression of lncRNA uc003fir increases proliferation, migration, and invasion of HTR-8/SVneo cells. [163]
FOXD2-AS1 placenta downregulated miR-3127/MMP2/MMP9 FOXD2-AS1 silencing decreases the promotion effects on trophoblast cell induced by miR-3127 inhibition, partly mediated by influencing MMP2 and MMP9 levels. [164]
KCNQ1OT1 placenta downregulated miR-146a-3p KCNQ1OT1 could target the regulation of miR-146a-3p through CXCL12/CXCR4 pathway in the proliferation, invasion and migration of HTR8/SVneo cells. [165]
SNHG5 placenta downregulated miR-26a-5p/N-cadherin Knockdown of SNHG5 inhibits trophoblast (HTR-8/SVneo) cell proliferation, invasion, and migration, and promotes apoptosis and caused increase of cell population at the G 0 /G 1 phase and decrease of cell population at the S phase. [166]
PVT1 placenta downregulated PI3K/AKT PVT1 knockdown notably inhibits the proliferation, migration and invasiveness abilities of trophoblast cells, and significantly promotes the apoptosis through PI3K/AKT pathway. [167]
Ezh2/ANGPTL4 PVT1 knockdown notably inhibits cell proliferation and stimulates cell cycle accumulation and apoptosis by repressing ANGPTL4 transcription through binding with EZH2 in trophoblast cell. [168]
WDR86-AS1 placenta upregulated miR-10b-3p / LITAF WDR86-AS1 downregulates miR-10b-3p but promotes LITAF expression, which controls the inflammatory responses and migration and proliferation of HTR-8/SVneo cells under hypoxia. [169]
ATB placenta downregulated / Down-regulated lncRNA-ATB decreased migration, proliferation, tube-formation of HTR-8/SVneo cells. [170]
RPAIN placenta upregulated C1q The increased RPAIN levels may contribute to the development of preeclampsia through regulating trophoblast proliferation, invasion and apoptosis via C1q. [171]
NR_002794 placenta upregulated / NR_002794 has suppressive effects on proliferation and migration, and results in an increased rate of apoptosis. [172]
MVIH placenta downregulated Jun-B The silencing of MVIH expression inhibits cell growth, migration, invasion, and angiogenesis in various trophoblast cell lines by modulating Jun-B protein expression. [173]
GASAL1 placenta downregulated SRSF1/mTOR/EBP1/Bcl-2/caspase-3 lncRNA GASAL1 interacts with SRSF1 to regulate the proliferative, invasive, and apoptotic abilities of trophoblast cells via the mTOR signaling pathway. [174]
MIR193BHG placenta upregulated / / [175]
PROX1-AS1 placenta upregulated / /
GATA3-AS1 placenta upregulated / /
00511 placenta downregulated miR-31-5p / HOXA7 Down-regulated lnc00511 suppresses proliferation, invasion and autophagy, and enhances apoptosis in trophoblast cells to mediate pre-eclampsia progression through modulating the miR-31-5p/homeobox protein A7 axis. [176]
placenta downregulated miR-29b-3p/ Cyr61 AP2γ mediates downregulation of lncRNA LINC00511 as a ceRNA suppresses trophoblast invasion, proliferation and migration by regulating miR-29b-3p/Cyr61 axis. [177]
AK002210 serum downregulated / AK002210 knockdown suppresses trophoblast invasion, proliferation and migration [178]
ZBTB39 placenta upregulated miR-210/THSD7A Upregulated LncZBTB39 suppresses trophoblast invasion and migration via antagonizing the inhibition of miR-210 on THSD7A expression. [179]
GAS5 placenta upregulated miR-21/MMP-9/TP53 GAS5 suppresses trophoblast invasion, proliferation and migration through the regulation of miR-21 and the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53. [180]
VIM-AS1 placenta downregulated E-cadherin/Snail/Vimentin Down-regulated VIM-AS1 suppresses epithelial-to-mesenchymal transition (EMT) by upregulating E-cadherin and downregulating Snail and Vimentin. [181]
FAM99A placenta downregulated Wnt/β-catenin Down-regulated FAM99A suppresses the invasive and migratory abilities of HTR-8/SVneo, and increases the apoptotic rate. [182]
HIF1A-AS2 placenta downregulated LSD1/PHLDA1 HIF1A-AS2 suppresses trophoblast cell invasion and proliferation through upregulating PHLDA1 expression. [183]
00261 placenta upregulated miR-558/TIMP4 Lnc00261 exerts the suppressive effects on the trophoblast invasion and migration via targeting miR-558/TIMP4 axis, which may involve in the pathogenesis of PE. [184]
Uc.294 placenta upregulated / Uc.294 inhibits proliferation, invasion and promotes apoptosis of trophoblast cells HTR-8/SVneo. [185]
PSG10P placenta upregulated miR-19a-3p/IL1RAP IL1RAP promotes the expression of caspase-3 but inhibits MMP9 to suppresses proliferation, migration, and invasion of trophoblast cells. [186]
00473 placenta downregulated LSD1/TFPI2 lnc00473 inhibits the expression of tissue factor pathway inhibitor 2 (TFPI2) through binding to lysine-specific demethylase 1 (LSD1) to inhibits cell proliferation and promotes apoptosis. [187]
Uc.187 placenta upregulated PCNA and Ki67/MMP-2/−9 / TIMP-1/ Bcl-2 Uc.187 suppresses cell proliferation and invasion and promotes the cellular apoptotic response [188]