Top

Journal of Assisted Reproduction and Genetics

Open Access 06-05-2024 | Pre-Eclampsia | Reproductive physiology and disease

LncRNA-NEAT1 blocks the Wnt/β-catenin signaling pathway by targeting miR-217 to inhibit trophoblast cell migration and invasion

Authors: Ling-ling Jiang, Dan-lin Yang, Qing Han, Hua-le Zhang, Mian Pan, Jian-ying Yan

Published in: Journal of Assisted Reproduction and Genetics

Abstract

Objective

This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE.

Methods

30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H₂O₂. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/β-catenin signaling pathway were detected using western blotting.

Results

The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/β-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and β-catenin, was significantly increased after siRNA-NEAT1.

Conclusions

NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE.

Agostinis C, Rami D, Zacchi P, Bossi F, Stampalija T, Mangogna A, et al. Pre-eclampsia affects procalcitonin production in placental tissue. Am J Reprod Immunol. 2018;79(4):e12823. https://doi.org/10.1111/aji.12823.CrossRefPubMed

Yang Y, Li H, Ma Y, Zhu X, Zhang S, Li J. MiR-221-3p is down-regulated in preeclampsia and affects trophoblast growth, invasion and migration partly via targeting thrombospondin 2. Biomed Pharmacother. 2019;109:127–34. https://doi.org/10.1016/j.biopha.2018.10.009.CrossRefPubMed

Hu J, Wang Z, Shan Y, Pan Y, Ma J, Jia L. Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/beta-catenin axis. Cell Death Dis. 2018;9(7):711. https://doi.org/10.1038/s41419-018-0746-z.CrossRefPubMedPubMedCentral

Zou Y, Jiang Z, Yu X, Sun M, Zhang Y, Zuo Q, et al. Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. PLoS ONE. 2013;8(11):e79598. https://doi.org/10.1371/journal.pone.0079598.CrossRefPubMedPubMedCentral

Zou Y, Li Q, Xu Y, Yu X, Zuo Q, Huang S, et al. Promotion of trophoblast invasion by lncRNA MVIH through inducing Jun-B. J Cell Mol Med. 2018;22(2):1214–23. https://doi.org/10.1111/jcmm.13400.CrossRefPubMed

GremLich S, Damnon F, Reymondin D, Braissant O, Schittny JC, Baud D, et al. The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development. Placenta. 2014;35(1):44–9. https://doi.org/10.1016/j.placenta.2013.11.003.CrossRefPubMed

Ye J, Xu M, Tian X, Cai S, Zeng S. Research advances in the detection of miRNA. J Pharm Anal. 2019;9(4):217–26. https://doi.org/10.1016/j.jpha.2019.05.004.CrossRefPubMedPubMedCentral

Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505(7483):344–52. https://doi.org/10.1038/nature12986.CrossRefPubMedPubMedCentral

Wang H, Ke J, Guo Q, Barnabo Nampoukime KP, Yang P, Ma K. Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis. J Cell Mol Med. 2018;22(12):5862–76. https://doi.org/10.1111/jcmm.13856.CrossRefPubMedPubMedCentral

10.

Chen DL, Zhang DS, Lu YX, Chen LZ, Zeng ZL, He MM, et al. microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer. Oncotarget. 2015;6(13):10868–79. https://doi.org/10.18632/oncotarget.3451.CrossRefPubMedPubMedCentral

11.

Duchartre Y, Kim YM, Kahn M. The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol. 2016;99:141–9. https://doi.org/10.1016/j.critrevonc.2015.12.005.CrossRefPubMed

12.

Leveno KJ. Williams manual of obstetrics. Williams manual of obstetrics; 2003.

13.

Starling S. A molecular signal for preeclampsia. Nat Rev Endocrinol. 2020;16(9):471. https://doi.org/10.1038/s41574-020-0397-x.CrossRefPubMed

14.

Fan X, Lou J, Zheng X, Wang Y, Wang J, Luo M, et al. Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression. Immunopharmacol Immunotoxicol. 2021;43(3):334–42. https://doi.org/10.1080/08923973.2021.1910834.CrossRefPubMed

15.

Hayder H, O’Brien J, Nadeem U, Peng C. MicroRNAs: crucial regulators of placental development. Reproduction. 2018;155(6):R259–71. https://doi.org/10.1530/REP-17-0603.CrossRefPubMed

16.

Anton L, DeVine A, Polyak E, Olarerin-George A, Brown AG, Falk MJ, et al. HIF-1alpha Stabilization Increases miR-210 Eliciting First Trimester Extravillous Trophoblast Mitochondrial Dysfunction. Front Physiol. 2019;10:699. https://doi.org/10.3389/fphys.2019.00699.CrossRefPubMedPubMedCentral

17.

Schaefer KN, Peifer M. Wnt/Beta-Catenin Signaling Regulation and a Role for Biomolecular Condensates. Dev Cell. 2019;48(4):429–44. https://doi.org/10.1016/j.devcel.2019.01.025.CrossRefPubMedPubMedCentral

18.

Krivega M, Essahib W, Van de Velde H. WNT3 and membrane-associated beta-catenin regulate trophectoderm lineage differentiation in human blastocysts. Mol Hum Reprod. 2015;21(9):711–22. https://doi.org/10.1093/molehr/gav036.CrossRefPubMed

Title: LncRNA-NEAT1 blocks the Wnt/β-catenin signaling pathway by targeting miR-217 to inhibit trophoblast cell migration and invasion
Authors: Ling-ling Jiang
Dan-lin Yang
Qing Han
Hua-le Zhang
Mian Pan
Jian-ying Yan
Publication date: 06-05-2024
Publisher: Springer US
Keyword: Pre-Eclampsia
Published in: Journal of Assisted Reproduction and Genetics
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-024-03124-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

LncRNA-NEAT1 blocks the Wnt/β-catenin signaling pathway by targeting miR-217 to inhibit trophoblast cell migration and invasion

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content