miR-193a-3p Mediates Placenta Accreta Spectrum Development by Targeting EFNB2 via Epithelial-Mesenchymal Transition Pathway Under Decidua Defect Conditions

Abstract

Objective: To clarify the role of microRNA-193a-3p (miR-193a-3p) in the pathogenesis of placenta accreta spectrum.Methods: The placental tissue expression levels of miR-193a-3p and Ephrin-B2 (EFNB2) were compared between a placenta accreta spectrum group and a control group. Transwell migration and invasion assays were used to verify the effect of miR-193a-3p and EFNB2 on HTR-8/SVneo cells cultured in human endometrial stromal cell (hESC)-conditioned medium. Epithelial-mesenchymal transition (EMT)-related proteins were examined by western blotting to establish whether the EMT pathway was altered in placenta accreta spectrum. To determine whether EFNB2 is a target gene of miR-193a-3p, luciferase activity assays were performed.Results: miR-193a-3p was upregulated but EFNB2 downregulated in the placenta accreta spectrum group and EFNB2 was a direct target of miR-193a-3p. Overexpression or inhibition of miR-193a-3p revealed that miR-193a-3p promoted the migration and invasion of HTR-8/SVneo cells cultured in hESC-conditioned medium. Furthermore, EMT was induced, as shown by increased N-cadherin, vimentin, MMP2, and MMP9 and decreased E-cadherin in the placenta accreta spectrum group and in HTR-8/SVneo cells transfected with miR-193a-3p mimics or si-EFNB2. The negative effect of miR-193a-3p inhibitor was reversed by co-transfection with si-EFNB2 in function studies and in analyses of EMT-related proteins in vitro.Conclusion: miR-193a-3p which upregulated in placenta accreta spectrum group increases HTR-8/SVneo cell migration and invasion by targeting EFNB2 via the EMT pathway under decidua defect conditions to lead to placenta accreta spectrum.

Overexpressed LAMC2 promotes trophoblast over‐invasion through the PI3K/Akt/MMP2/9 pathway in placenta accreta spectrum

“…However, the specific role of these molecules in the pathogenesis of PAS has not been completely elucidated. [9][10][11] Hence, it is imperative to identify the relevant proteins and pathways affecting placental implantation for further prediction and intervention. Laminins are in the basement membrane protein family and prior studies have shown that laminins are engaged in placental development and regulate placental trophoblast cell functions.…”

“…The accumulating evidences have confirmed that molecular and phenotypic similarities between PAS and cancer. However, the specific role of these molecules in the pathogenesis of PAS has not been completely elucidated 9–11 . Hence, it is imperative to identify the relevant proteins and pathways affecting placental implantation for further prediction and intervention.…”

Analysis of serum circulating MicroRNAs level in Malaysian patients with gestational diabetes mellitus

“…Furthermore, our finding was in an agreement with Yang et al in which we found that miR-23a could function as a potential biomarker in the first trimester of GDM. On the other hand, upregulated miR193a has been shown to play a vital role in the pathogenesis of placenta accreta spectrum development mediated by the target in EFNB2 gene via the EMT signaling pathway 26 . In addition to that, elevated miR193a was reported as a potentially new biomarker for the diagnosis of diabetic nephropathy 27 .…”

Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detection

“… 21 , 22 , 23 In cases of PAS, several miRs play a role in pathogenesis, including miR-34a, -125a, -193a, and -518b. 24 , 25 , 26 , 27 However, miR data for PAS are limited. Chen et al 28 have shown potential benefit in using a 4 miR PAS signature in a small cohort of patients with placenta increta or percreta.…”