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miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9.
Biofactors 2017; 43(2):210-219B

Abstract

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Department of Economics, National Cheng Kung University, Tainan, Taiwan.Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27619846

Citation

Su, Mei-Tsz, et al. "MiR-346 and miR-582-3p-regulated EG-VEGF Expression and Trophoblast Invasion Via Matrix Metalloproteinases 2 and 9." BioFactors (Oxford, England), vol. 43, no. 2, 2017, pp. 210-219.
Su MT, Tsai PY, Tsai HL, et al. MiR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9. Biofactors. 2017;43(2):210-219.
Su, M. T., Tsai, P. Y., Tsai, H. L., Chen, Y. C., & Kuo, P. L. (2017). MiR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9. BioFactors (Oxford, England), 43(2), pp. 210-219. doi:10.1002/biof.1325.
Su MT, et al. MiR-346 and miR-582-3p-regulated EG-VEGF Expression and Trophoblast Invasion Via Matrix Metalloproteinases 2 and 9. Biofactors. 2017;43(2):210-219. PubMed PMID: 27619846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9. AU - Su,Mei-Tsz, AU - Tsai,Pei-Yin, AU - Tsai,Hui-Ling, AU - Chen,Yi-Chi, AU - Kuo,Pao-Lin, Y1 - 2016/09/13/ PY - 2016/04/11/received PY - 2016/07/14/revised PY - 2016/08/09/accepted PY - 2016/9/14/pubmed PY - 2017/5/10/medline PY - 2016/9/14/entrez KW - EG-VEGF (prokineticin 1) KW - cell invasion KW - matrix metalloproteinase (MMP) KW - miR-346 KW - miR-582-3p SP - 210 EP - 219 JF - BioFactors (Oxford, England) JO - Biofactors VL - 43 IS - 2 N2 - Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017. SN - 1872-8081 UR - https://www.unboundmedicine.com/medline/citation/27619846/miR_346_and_miR_582_3p_regulated_EG_VEGF_expression_and_trophoblast_invasion_via_matrix_metalloproteinases_2_and_9_ L2 - https://doi.org/10.1002/biof.1325 DB - PRIME DP - Unbound Medicine ER -