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miR-219a suppresses human trophoblast cell invasion and proliferation by targeting vascular endothelial growth factor receptor 2 (VEGFR2)

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Objective

Vascular endothelial growth factor (VEGF) plays a critical role in regulating trophoblast cell invasion and proliferation, involved in a variety of pregnancy complications, such as spontaneous abortion and pre-eclampsia. Numerous studies have revealed that microRNAs (miRNAs) are participated in a series of molecular processes that regulate cell function, such as cell invasion, proliferation, and apoptosis. Vascular endothelial growth factor receptor 2 (VEGFR2), a receptor of VEGF, has been shown to be involved in trophoblast function. However, the relation between miRNA and VEGFR2 and their role in trophoblast function remain to be elucidated.

Methods

The effect of miR-219a on the trophoblast function has been explored using luciferase reporter, transwell, qRT-PCR, western blot, bromodeoxyuridine (BrdU), ELISA, immunofluorescent staining, and tube formation assays.

Results

In the current study, we observed that through targeted inhibition of VEGFR2 expression by miR-219a, the function of VEGFR2 as well as the downstream PI3K/AKT/NF-κB signaling pathway were suppressed, leading to suppression of trophoblastic proliferation and invasion. Moreover, upregulation of VEGFR2 restored the miR-219a–inhibited cell proliferation, invasion, and tube formation.

Conclusions

These results revealed that miR-219a played crucial roles in negatively regulating trophoblastic proliferation and invasion by suppression of the PI3K/AKT/NF-κB signaling pathway by targeting VEGFR2, therefore serving as a potential treatment method for the complications of pregnancy caused by trophoblastic dysregulation.

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Acknowledgments

This work was supported by the Natural Science Foundation of Anhui Province (1708085MH214).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, 230000, Hefei, People’s Republic of China

    Guiju Zhou, Pin Hu, Jing Wang, Juanjuan Fu, Bing Wei & Yu Zhang

  2. Anqing Municipal Hospital, Anhui Medical University, Anqing, China

    Zhifang Li

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  1. Guiju Zhou
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Correspondence to Bing Wei or Yu Zhang.

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Zhou, G., Li, Z., Hu, P. et al. miR-219a suppresses human trophoblast cell invasion and proliferation by targeting vascular endothelial growth factor receptor 2 (VEGFR2). J Assist Reprod Genet 38, 461–470 (2021). https://doi.org/10.1007/s10815-020-02022-y

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