Table 4 Dysregulation of lncRNAs in PE

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]