Mesenchymal Stem Cells-Derived Exosomal H19 Promotes Trophoblast Cell Invasion and Migration by Down-Regulating Let-7b in Preeclampsia

Abstract

Aberrant expression of long non-coding RNAs (lncRNAs) was associated with tumorigenesis and other diseases. As transport carriers, cells-derived exosomes were released into the extracellular space and regulated multiple functions of target cells. The present study aimed to investigate the clinical significance and biological function of mesenchymal stem cells (MSCs)-derived exosomal H19 in preeclampsia (PE). The expression of let-7b and FOXO1 in PE placental tissues was measured by RNA quantification and Western blot assay. Interaction between FOXO1 and let-7b, as well as let-7b and H19 was identified by dual luciferase reporter gene assay, and further confirmed by RNA-pull down and RNA immunoprecipitation assays. The roles of let7b and FOXO1 in trophoblast cells were tested by gain- or loss-of-function experiments. Exosomes derived from MSCs were isolated and co-cultured with HTR-8/SVNEO cells, and the invasion, migration, and apoptosis of trophoblast cells were measured in response to overexpression or silence of H19. The expression of let-7b was increased and FOXO1 was decreased in placental tissues of PE patients. H19 competitive bound to let-7b by acting as a competitive endogenous RNA (ceRNA), and FOXO1 was a target gene of let-7b. Then, H19 was delivered to HTR-8/SVNEO cells by MSCs-secreted exosomes. MSCs-derived exosomes overexpressing H19 up-regulated FOXO1 and activated AKT signaling pathway by silence of let-7b, thus to promote invasion, migration and suppress apoptosis of trophoblast cells in PE. Collectively, the key findings of the present study provided an evidence that functional up-regulation of MSCs-derived exosomes containing H19 enhanced invasion, migration and suppressed apoptosis of trophoblast cells in PE. Funding Statement: This study was supported by the Department of Science and Technology of Jilin Province (20170204045SF). Declaration of Interests: The authors declare no competing interests. Ethical Approval Statement: The study was conducted under the approval of the Ethics Committee of The Second Hospital of Jilin University. All participating patients signed informed consent documentation. All experiments were conducted in strict accordance with the Helsinki Declaration.