title: Aberrantly up-regulated miR-20a in pre-eclampsic placenta compromised the proliferative and invasive behaviors of trophoblast cells by targeting forkhead box protein A1.
abstract: Preeclampsia is a serious complication in pregnancy. Dysregulation of trophoblast cell proliferation and invasion is a major pathological alteration observed in preeclampsia. Recently, microRNAs were shown to participate in the pathogenesis of preeclampsia. In this study we explored the effect of miR-20a on the proliferation and invasion of trophoblast cells and the underlying mechanism. We verified the distribution of miR-20a in human placenta by in situ hybridization. Real time PCR data showed that the level of miR-20a increased by 2.6 folds in human preeclampsia than normal tissues. We then cultured trophoblast-like JEG-3 cells and evaluated the effect of miR-20a on JEG-3 cell proliferation, migration and invasion. Overexpression of miR-20a significantly inhibited the proliferation, migration and invasion of cultured JEG-3 cells, which were abolished by co-transfection of AMO-20a. Transfection of miR-20a also inhibited JEG-3 cell xenograft tumor growth in nude mice. Luciferase assay technique was used to identify the direct regulation of miR-20a on Forkhead Box Protein A1(FOXA1). Transfection of miR-20a markedly reduced the luciferase activity of the chimeric plasmid containing the 3'UTR of FOXA1, indicating FOXA1 is the target of miR-20a. Furthermore, transfection of miR-20a inhibited both protein and mRNA expression of FOXA1 in JEG-3 cells. In summary, the upregulated miR-20a in human preeclampsia tissue can inhibit the proliferative and invasive activities of trophoblast cells by repressing the expression of FOXA1.
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1. Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;
authors.forename: Junxiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yingzhe
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2. Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.affiliation: 1. Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;
authors.forename: Shanshun
authors.initials: S
authors.lastname: Luo
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; C534451:MIRN20a microRNA, human; D035683:MicroRNAs
keywords: FOXA1; invasion; miR-20a; migration; proliferation.