title: MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.
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: 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.
authors: Jie
authors: J
authors: Ding
authors: Department of Stomatology, PLA Navy General Hospital, Beijing 100048, China.
authors: Fei
authors: F
authors: Huang
authors: Department of Stomatology, Jinan General Military Hospital, Jinan 250000, China.
authors: Gaoyi
authors: G
authors: Wu
authors: Department of Orthopedics, Hainan Branch of PLA General Hospital, Hainan 572013, China.
authors: Tao
authors: T
authors: Han
authors: Department of Gynecology and Obstetrics, Shijingshan Hospital, Beijing 100043, China.
authors: Fuqiang
authors: F
authors: Xu
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors: Dan
authors: D
authors: Weng
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors: Chengli
authors: C
authors: Wu
authors: 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.
authors: Xiaodong
authors: X
authors: Zhang
authors: 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.
authors: Yuanqing
authors: Y
authors: Yao
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors: Xiaoming
authors: X
authors: Zhu
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C546194:MIRN519 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2