MiR-141-3p downregulation promotes tube formation, migration, invasion and inhibits apoptosis in hypoxia-induced human umbilical vein endothelial cells by targeting Notch2.

Abstract

Vascular endothelial cell damage is regarded as the carrier in the progression of the pathological changes of preeclampsia (PE) from the placenta to maternal organs. MicroRNA (miR)-141-3p was aberrantly expressed during PE pathogenesis. We investigated the role of miR-141-3p in regulating the biological behaviors of endothelial cells in PE. Human umbilical vein endothelial cells (HUVECs) were isolated from the human umbilical cords and cultured under hypoxia condition to establish PE models. The binding of miR-141-3p and Notch2 was confirmed by dual-luciferase reporter assay. HUVECs were transfected with miR-141-3p inhibitor and siRNA-Notch2. The viability, vascularization capability, migration, and invasion of HUVECs were evaluated by MTT, tube formation, and Transwell assays. Cell apoptosis was measured via flow cytometry. The expressions of miR-141-3p, Notch2, Bcl-2, Bax and cleaved caspase-3 were assessed by qRT-PCR or Western blot. MiR-141-3p expression was upregulated in the HUVECs isolated from PE tissues and hypoxia-induced HUVECs. Hypoxia treatment inhibited viability, tube formation, migration, and invasion, and promoted apoptosis in HUVECS, as well as increased Bax and cleaved caspase-3 expressions and decreased Bcl-2 expression. Downregulating miR-141-3p expression promoted viability, tube formation, migration and invasion, and inhibited apoptosis in HUVECs, counteracting the effect of hypoxia on HUVECs. MiR-141-3p directly targeted Notch2. Silencing Notch2 reversed the promoting effect of downregulated miR-141-3p expression on HUVECs. In conclusion, downregulating miR-141-3p expression during hypoxia promotes tube formation, migration, and invasion and inhibits apoptosis in HUVECs by targeting Notch2.

• Authors: Zhonghui Ling, Min Chen, Ting Li, Yating Qian, Chanjuan Li
• Journal: Reproductive biology (Reprod Biol) Vol. 21 Issue 2 Pg. 100483 (Jun 2021) ISSN: 2300-732X [Electronic] Poland
• PMID: 33631423 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.

Chemical References

• MIRN141 microRNA, human
• MicroRNAs
• NOTCH2 protein, human
• Receptor, Notch2
• Oxygen

Topics

• Apoptosis (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation
• Down-Regulation (drug effects)
• Gene Expression Regulation
• Human Umbilical Vein Endothelial Cells
• Humans
• MicroRNAs (genetics, metabolism)
• Neovascularization, Physiologic (drug effects)
• Oxygen (pharmacology)
• Receptor, Notch2 (genetics, metabolism)
• Up-Regulation