Downregulation of MicroRNA-125a in Placenta Accreta Spectrum Disorders Contributes Antiapoptosis of Implantation Site Intermediate Trophoblasts by Targeting MCL1.

ABSTRACT

The typical hallmark of placenta accreta spectrum (PAS) disorders is increased implantation site intermediate trophoblast (ISIT) cell numbers. However, the extent of trophoblast proliferation and apoptosis have not been found to differ from those of normal placentation. MicroRNA-125a (miR-125a) induces apoptosis in colon cancer cell by targeting myeloid cell leukemia-1 gene (MCL1). We aimed to investigate the influence of miR-125a on ISIT cells in PAS disorders in 15 patients (self-paired trials) with placenta previa and PAS disorders. Expression of miR-125a and MCL1 were measured in villous trophoblasts and basal plate myometrial fibers from creta site and adjacent noncreta tissues by real-time quantitative polymerase chain reaction, and expression of the MCL1 protein was assayed by Western blotting. Flow-cytometry was used to examine the effect of miR-125a overexpression on apoptosis in vitro in HTR-8/SVneo cells, and luciferase activity assays was used to confirm miR-125a targeting of MCL1. In vivo, the expression levels of miR-125a was significantly lower in creta versus noncreta tissues, and the expression of MCL1 was upregulated; moreover, immunohistochemistry showed that the increased ISIT cells in the creta were positive for MCL1 protein. MCL1 was downregulated in the miR-125a-overexpressing HTR-8/SVneo cells in vitro, and overexpression of miR-125a-induced apoptosis in the HTR-8/SVneo trophoblast line. Finally, luciferase activity assays confirmed that miR-125a directly target the 3' untranslated region of MCL1 in the 293T cell line. In conclusion, downregulation of MCL1-targeting miR-125a exerts an antiapoptotic effect on ISIT cells in PAS disorders.