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

journal contribution
posted on 07.04.2020, 15:32 by Jing Tian, Yamin Liu, Mingyu Hu, Yangxi Zheng, Ping Xu, Lan Zhang, Jiujiang Liao, Yue Wu, Li Wen, Chao Tong, Jianying Yan, Hongbo Qi, Richard Saffery, Philip N Baker, Mark D Kilby
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.

Funding

This work was supported by grants from the National Natural Sciences Foundation of China (81520108013, 81771613, 81671488, 81871189), and the Commission of Science and Technology of Chongqing Municipality (cstc2017jcyjBX0045). We also would like to acknowledge the support from the “111 program” of the Ministry of Education P.R.C. and State Administration of Foreign Experts Affairs P.R.C., and the State International Collaborative Laboratory of Reproduction and Development.

History

Citation

European Journal of Obstetrics & Gynecology and Reproductive Biology Volume 248, May 2020, Pages 164-171

Version

AM (Accepted Manuscript)

Published in

European journal of obstetrics, gynecology, and reproductive biology

Volume

248

Pagination

164 - 171

Publisher

Elsevier BV

issn

0301-2115

eissn

1872-7654

Acceptance date

16/03/2020

Copyright date

2020

Available date

19/03/2020

Publisher version

https://www.sciencedirect.com/science/article/pii/S0301211520301512

Language

eng

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