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.

中文翻译：

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miR-219a 通过靶向血管内皮生长因子受体 2 (VEGFR2) 抑制人滋养层细胞的侵袭和增殖

客观的

血管内皮生长因子（VEGF）在调节滋养层细胞的侵袭和增殖中起关键作用，涉及多种妊娠并发症，如自然流产和先兆子痫。大量研究表明，microRNAs (miRNAs) 参与了一系列调节细胞功能的分子过程，如细胞侵袭、增殖和凋亡。血管内皮生长因子受体 2 (VEGFR2) 是 VEGF 的一种受体，已被证明与滋养层功能有关。然而，miRNA 和 VEGFR2 之间的关系及其在滋养层功能中的作用仍有待阐明。

方法

已经使用荧光素酶报告基因、transwell、qRT-PCR、蛋白质印迹、溴脱氧尿苷 (BrdU)、ELISA、免疫荧光染色和管形成测定探索了 miR-219a 对滋养层功能的影响。

结果

在目前的研究中，我们观察到通过 miR-219a 靶向抑制 VEGFR2 的表达，VEGFR2 的功能以及下游的 PI3K/AKT/NF-κB 信号通路受到抑制，从而抑制滋养细胞的增殖和侵袭。此外，VEGFR2 的上调恢复了 miR-219a 抑制的细胞增殖、侵袭和管形成。

结论

这些结果表明，miR-219a 通过靶向 VEGFR2 抑制 PI3K/AKT/NF-κB 信号通路，在负调节滋养细胞增殖和侵袭中起关键作用，因此可作为滋养细胞失调引起的妊娠并发症的潜在治疗方法。 .