Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells - 04/04/18
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Graphical abstract |
Abstract |
Background |
Preeclampsia (PE), characterized by hypertension and proteinuria, is a leading cause of perinatal and maternal mortality. Considering that mutation of H19 gene is closely associated with PE, we aimed to explore the functional role of long non-coding RNA H19 (lncRNA-H19) in trophoblast cells.
Methods |
Expression of lncRNA-H19 in placenta tissues from patients with PE and healthy pregnant women after delivery was determined by quantitative reverse transcription PCR. Then, lncRNA-H19 was abnormally expressed in JEG-3 and HTR-8 cells by stable cell transfection. Cell viability and invasion were assessed by using CCK-8 and Matrigel-coated Millicell system, respectively. Expression of key proteins associated with invasion and autophagy as well as key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathways were measured by Western blot analysis. Number of GFP-labeled autophagosomes was counted under a confocal microscope.
Results |
Level of lncRNA-H19 in the placenta tissues from PE patients was higher than that from healthy controls. LncRNA-H19 overexpression reduced cell viability but increased invasion of JEG-3 and HTR-8 cells. LncRNA-H19 silence showed the opposite effects. In addition, lncRNA-H19 overexpression promoted autophagy in trophoblast cells. Furthermore, phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathways were enhanced by lncRNA-H19 overexpression while were reduced by lncRNA-H19 silence.
Conclusion |
LncRNA-H19, which was up-regulated in PE, reduced cell viability but promoted invasion and autophagy in trophoblast cells, along with activation of the PI3K/AKT/mTOR pathways. Our study provides a theoretical basis for pathogenesis of PE, aiding to identification of novel therapeutic strategies for PE.
Le texte complet de cet article est disponible en PDF.Keywords : Preeclampsia, lncRNA-H19, Viability, Invasion, Autophagy, PI3K/AKT/mTOR
Plan
Vol 101
P. 691-697 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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