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MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.
PLoS One 2015; 10(3):e0120321Plos

Abstract

Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE) is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2) is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China; The 307th Hospital of Chinese People's Liberation Army, the affiliated Hospital of Military Medical Science, Beijing 100071, China.Department of Stomatology, PLA Navy General Hospital, Beijing 100048, China.Department of Stomatology, Jinan General Military Hospital, Jinan 250000, China.Department of Orthopedics, Hainan Branch of PLA General Hospital, Hainan 572013, China.Department of Gynecology and Obstetrics, Shijingshan Hospital, Beijing 100043, China.Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China; Department of Obstetrics and Gynecology, PLA General Hospital, Beijing 100853, China.Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25803859

Citation

Ding, Jie, et al. "MiR-519d-3p Suppresses Invasion and Migration of Trophoblast Cells Via Targeting MMP-2." PloS One, vol. 10, no. 3, 2015, pp. e0120321.
Ding J, Huang F, Wu G, et al. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. PLoS ONE. 2015;10(3):e0120321.
Ding, J., Huang, F., Wu, G., Han, T., Xu, F., Weng, D., ... Zhu, X. (2015). MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. PloS One, 10(3), pp. e0120321. doi:10.1371/journal.pone.0120321.
Ding J, et al. MiR-519d-3p Suppresses Invasion and Migration of Trophoblast Cells Via Targeting MMP-2. PLoS ONE. 2015;10(3):e0120321. PubMed PMID: 25803859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. AU - Ding,Jie, AU - Huang,Fei, AU - Wu,Gaoyi, AU - Han,Tao, AU - Xu,Fuqiang, AU - Weng,Dan, AU - Wu,Chengli, AU - Zhang,Xiaodong, AU - Yao,Yuanqing, AU - Zhu,Xiaoming, Y1 - 2015/03/24/ PY - 2015/01/24/received PY - 2015/02/08/accepted PY - 2015/3/25/entrez PY - 2015/3/25/pubmed PY - 2016/2/26/medline SP - e0120321 EP - e0120321 JF - PloS one JO - PLoS ONE VL - 10 IS - 3 N2 - Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE) is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2) is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25803859/MiR_519d_3p_suppresses_invasion_and_migration_of_trophoblast_cells_via_targeting_MMP_2_ L2 - http://dx.plos.org/10.1371/journal.pone.0120321 DB - PRIME DP - Unbound Medicine ER -