Upregulated LncZBTB39 in pre-eclampsia and its effects on trophoblast invasion and migration via antagonizing the inhibition of miR-210 on THSD7A expression

Tian, Jing, Liu, Yamin, Hu, Mingyu, Zheng, Yangxi, Xu, Ping, Zhang, Lan, Liao, Jiujiang, Wu, Yue, Wen, Li, Tong, Chao, Yan, Jianying, Qi, Hongbo, Saffery, Richard, Baker, Philip N. and Kilby, Mark D. (2020) Upregulated LncZBTB39 in pre-eclampsia and its effects on trophoblast invasion and migration via antagonizing the inhibition of miR-210 on THSD7A expression. European Journal of Obstetrics and Gynecology and Reproductive Biology, 248. pp. 164-171. ISSN 0301-2115

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Abstract

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 human placentas, 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.

Item Type: Article
Uncontrolled Keywords: invasion,lnczbtb39,pre-eclampsia,trophoblast,reproductive medicine,obstetrics and gynaecology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2743
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 11 Jun 2025 14:30
Last Modified: 13 Jun 2025 15:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/99473
DOI: 10.1016/j.ejogrb.2020.03.035

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