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Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia
Institution:1. Department of Obstetrics, Jingmen First People''s Hospital, Jingmen City, 448000, Hubei Province, China;2. Department of Gynecology, Jingmen First People''s Hospital, Jingmen City, 448000, Hubei Province, China;1. Centre for Human Reproductive Science (ChRS), Institute of Metabolism and Systems Research, College of Medical & Dental Sciences, University of Birmingham, United Kingdom;2. Birmingham Women’s Fertility Centre, Birmingham Women’s Hospital, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, United Kingdom;3. School of Biosciences, University of Birmingham, United Kingdom;1. Department of Obstetrics, The Maternity Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, China;2. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China;3. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China;4. The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China;5. Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China;6. Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, 530021, China;1. Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Wuhan, 430064, Hubei, China;2. Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture), Wuhan, 430064, Hubei, China;3. College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China;1. Department of Obstetrics and Gynaecology, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Centre, University of Szeged, Szeged, Hungary;2. Department of Laboratory Medicine, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Centre, University of Szeged, Szeged, Hungary;3. Department of Obstetrics and Gynaecology, Danderyd Hospital, Stockholm, Sweden;1. Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, Guangdong, China;2. Department of Paediatrics, Affliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, 518055, Guangdong, China
Abstract:Preeclampsia (PE) is the leading cause of maternal deaths in primipara. It is mainly characterized by defect migration and invasion of trophoblast cells. Circular RNAs (circRNAs) have been widely reported to be associated with PE progression. This study is designed to explore the role and mechanism of circ_0032962 on trophoblast cell behavior. Circ_0032962, microRNA-326 (miR-326), and Pre-B-cell leukemia homeobox 3 (PBX3) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, migration, and invasion were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), Colony formation, wound healing, and transwell assays. Protein levels of E-cadherin, Vimentin, N-cadherin, and PBX3 were examined by western blot assay. The binding relationship between miR-326 and circ_0032962 or PBX3 was predicted by circular RNA Interactome or Starbase and then verified by a dual-luciferase reporter assay. Circ_0032962 and PBX3 levels were declined in placenta tissues from preeclampsia patients, and miR-326 was elevated. Apart from that, circ_0032962 knockdown could suppress cell proliferation ability, migration, invasion, and epithelial-mesenchymal transition (EMT) in trophoblast cells. Mechanically, circ_0032962 could affect PBX3 expression through sponging miR-326. Circ_0032962 could contribute to trophoblast cell growth ability and metastasis partly by regulating the miR-326/PBX3 axis, providing a novel insight into the pathogenesis and treatment of PE.
Keywords:circ_0032962  miR-326  PBX3  Preeclampsia  Trophoblast cells
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