title: Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1.
abstract: Placenta accreta is defined as abnormal adhesion of placental villi to the uterine myometrium. Although this condition has become more common as a result of the increasing rate of cesarean sections, the underlying causative mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been shown to play important roles in placental development, this study evaluated the roles of these microRNAs in placenta accreta.
  
  
  
  Expression of miR-29a/b/c and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain reaction. Western blotting was used to analyze expression of the MCL1 protein in HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays were used to determine whether MCL1 is a target gene of miR-29a/b/c.
  
  
  
  Expression of miR-29a/b/c was significantly lower in creta sites compared to noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p = 0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that miR-29a/b/c directly target the 3' untranslated region of MCL1 in 293T cells. Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast cell line. Moreover, histopathological evaluation revealed that the number of implantation site intermediate trophoblast (ISIT) cells was increased in creta sites and that these cells were positive for MCL1.
  
  
  
  Our results demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT cells by targeting MCL1. These findings provide new insights into the pathogenesis of placenta accreta.
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
authors.forename: Xietong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
authors.forename: Changting
authors.initials: C
authors.lastname: Zuo
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
authors.forename: Jinlai
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Yunnan
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China; Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China. Electronic address: yyy306@126.com.
authors.forename: Junhao
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China; Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, China; Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China. Electronic address: chenzijiang@hotmail.com.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D010064:Embryo Implantation / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D010921:Placenta Accreta / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: C579095:MCL1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein
keywords: Apoptosis; Intermediate trophoblast; MCL1; Placenta accreta; microRNA-29a/b/c