Int J Biol Sci 2014; 10(9):973-982. doi:10.7150/ijbs.9088
Aberrantly Up-regulated miR-20a in Pre-eclampsic Placenta Compromised the Proliferative and Invasive Behaviors of Trophoblast Cells by Targeting Forkhead Box Protein A1
1. Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China;
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.
* Equal contributions to the work.
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.
Keywords: FOXA1, invasion, miR-20a, migration, proliferation.
Wang Y, Zhang Y, Wang H, Wang J, Zhang Y, Wang Y, Pan Z, Luo S. Aberrantly Up-regulated miR-20a in Pre-eclampsic Placenta Compromised the Proliferative and Invasive Behaviors of Trophoblast Cells by Targeting Forkhead Box Protein A1. Int J Biol Sci 2014; 10(9):973-982. doi:10.7150/ijbs.9088. Available from http://www.ijbs.com/v10p0973.htm