期刊
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
卷 248, 期 -, 页码 164-171出版社
ELSEVIER
DOI: 10.1016/j.ejogrb.2020.03.035
关键词
Invasion; lncZBTB39; Pre-eclampsia; Trophoblast
资金
- National Natural Sciences Foundation of China [81520108013, 81771613, 81671488, 81871189]
- Chongqing Science and Technology Commission [cstc2017jcyjBX0045]
- Ministry of Education P.R.C.
- State Administration of Foreign Experts Affairs P.R.C.
- State International Collaborative Laboratory of Reproduction and Development
Objective: Pre-eclampsia (PE) is a major cause of maternal morbidity and mortality, but its etiology remains to be elucidated. Accumulating evidence suggests that placental long noncoding RNAs (lncRNAs) might contribute to the pathogenesis of pre-eclampsia. Study Design: In the present study, the expression levels of lncRNAs in human placenta were first determined by microarray analysis and then validated by secondary RT-qPCR and FISH. LncZBTB39 expression manipulation in HTR8/SVneo trophoblast cells was achieved by shRNA and plasmid transfection. Then, the invasion and migration of lncZBTB39-deficient and lncZBTB39-overexpressing trophoblast cells were evaluated by transwell assays and wound-healing assays, respectively. MMP2 activity was measured by gelatin zymography. The downstream target genes of lncZBTB39 were then identified by a transcriptomic microarray, followed by RT-qPCR validation. Results: We found that lncZBTB39 was upregulated in PE-complicated humanplacentas, and overexpression of lncZBTB39 inhibited invasion and migration, as well as MMP2 activity in HTR8/SVneo cells, while downregulation of lncZBTB39 enhanced invasion, migration and MMP2 activity. In addition, THSD7A expression was elevated by lncZBTB39 overexpression but reduced in lncZBTB39-deficient cells; moreover, lncZBTB39 antagonized the inhibitory effects of miR-210 on THSD7A expression. Conclusion: PE-complicated placentas are associated with upregulated lncZBTB39, which negatively regulates trophoblast invasion and migration, most likely by preserving the expression of THSD7A mRNA through sponging miR-210. The results of this study not only provide novel evidence that lncRNAs regulate trophoblastic activities but also suggest that lncZBTB39 may be a potential interventional target for PE. (C) 2020 Elsevier B.V. All rights reserved.
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