The decreased lncRNA ZEB2‐AS1 in pre‐eclampsia controls the trophoblastic cell line HTR‐8/SVneo's invasive and migratory abilities via the miR‐149/PGF axis

Abstract

Pre‐eclampsia (PE) is a pregnancy disease that causes maternal death and threatens the health of newborns. Accumulating evidence has revealed the essential roles of long noncoding RNAs (lncRNAs) in the progression of PE. The present investigation determined lncRNA ZEB2 antisense RNA 1 (ZEB2‐AS1) expression in PE and looked into the potential role of ZEB2‐AS1 in modulating trophoblastic cell functions. Quantitative real‐time polymerase chain reaction evaluated gene expression. Western blot analyzed the placental growth factor (PGF) protein level. Cell counting kit‐8 and Transwell invasion assays assessed the proliferative and invasive abilities of placental trophoblast cells, respectively. Wound healing assay determined cell migratory potentials. Dual‐luciferase reporter assay assessed the targeting relationship among ZEB2‐AS1, miR‐149, and PGF. Downregulation of lncRNA ZEB2‐AS1 was detected in placentas from patients with PE when compared with those from normal pregnancies. Moreover, ZEB2‐AS1 upregulation markedly promoted proliferative, migratory, and invasive potentials in HTR‐8/SVneo cells, while knockdown of ZEB2‐AS1 had the opposite effects. The effects on HTR‐8/SVneo cells mediated by ZEB2‐AS1 was correlated with the miR‐149/PGF axis. These findings indicate that ZEB2‐AS1 contributes to PE progression by affecting cell proliferative and invasive capacities via the miR‐149/PGF axis in HTR‐8/SVneo cells. In sum, we identified that ZEB2‐AS1 was a novel aberrantly expressed lncRNA in the placentas of PE patients and lncRNA ZEB2‐AS1 modulated trophoblastic cell line HTR‐8/SVneo's proliferative and invasive potentials via targeting the miR‐149/PGF axis.

Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway

“…26 Meanwhile, another study has revealed that inhibition of miR-149 strengthened cell invasive and migratory potentials of trophoblasts in preeclampsia. 27 Moreover, the functions of miR-149 in human diseases have been explored. Yang et al have identified elevated miR-149-5p in non-small cell lung cancer tissues with the application of either small RNA-sequencing or RT-qPCR.…”

“…35 Another study has demonstrated binding sites between PGF 3 0 -UTR and miR-149, and PGF was decreased in HTR-8/SVneo cells upon treatment of miR-149 mimic, while its expression was restored in trophoblasts with miR-149 inhibitor transfection. 27 Furthermore, as for the correlation of miR-149 with the PTEN/Akt signaling pathway, an article has demonstrated that miR-149 exerted its biological functions in ovarian cancer cells through the modulation of the PI3K/Akt axis. 36 However, how miR-149 regulated the PTEN/Akt signaling pathway in RM needs deep verification.…”

“…An article has revealed that higher miR‐149 T > C polymorphism was detected in idiopathic recurrent pregnancy loss cases in contrast to healthy controls 26 . Meanwhile, another study has revealed that inhibition of miR‐149 strengthened cell invasive and migratory potentials of trophoblasts in preeclampsia 27 . Moreover, the functions of miR‐149 in human diseases have been explored.…”

“…For instance, a research was launched to elucidate whether ENG was involved in trophoblast invasion modulated by miR‐149‐5p, and the results of which outlined that there was a binding site between ENG and miR‐149‐5p in human trophoblasts 35 . Another study has demonstrated binding sites between PGF 3′‐UTR and miR‐149, and PGF was decreased in HTR‐8/SVneo cells upon treatment of miR‐149 mimic, while its expression was restored in trophoblasts with miR‐149 inhibitor transfection 27 . Furthermore, as for the correlation of miR‐149 with the PTEN/Akt signaling pathway, an article has demonstrated that miR‐149 exerted its biological functions in ovarian cancer cells through the modulation of the PI3K/Akt axis 36 .…”

Roles of noncoding RNAs in preeclampsia

“… [ 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.…”