Downregulation of MicroRNA-125a in Placenta Accreta Spectrum Disorders Contributes Antiapoptosis of Implantation Site In
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Downregulation of MicroRNA-125a in Placenta Accreta Spectrum Disorders Contributes Antiapoptosis of Implantation Site Intermediate Trophoblasts by Targeting MCL1
Reproductive Sciences 1-8 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119828040 journals.sagepub.com/home/rsx
Yongzhong Gu, MD1, Jinlai Meng, MD1, Changting Zuo, MD1, Shan Wang, MD1, Hongyan Li, MD1, Shigang Zhao, MD2,3,4, Tao Huang, MD2,3,4, Xietong Wang, MD1,5,6 , and Junhao Yan, MD1,2,3,4
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 30 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. Keywords placenta accreta spectrum, microRNA-125a, MCL1, intermediate trophoblast, antiapoptosis
Introduction Placenta accreta spectrum (PAS) disorders, which comprises placenta accreta, increta, and percreta, occurs when the placenta fails to detach from the uterine wall because of abnormal implantation at the basal plate.1 Rising numbers of cesarean deliveries are largely responsible for the increasing prevalence of PAS disorders,2 and recent data show that China has the highest overall rate (46.2%) of caesarean sections.3 The Chinese government launched the “universal 2-child policy” in 2015 to allow all couples to have a second child. This put an end to the nation’s strict 1-child restriction, and it has resulted in an increase in the number of multiparous woman with a prior cesarean delivery, this implies a high prevalence of PAS disorders
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