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Updated: Oct 25, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DEAD-box helicase 6 (DDX6) under hypoxia
Zhongyan Zhao1, Chanji Wu1, Xiangying He1
1Department of Neurology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China.
Abstract:
Stroke is a main cause of disability and death worldwide, and ischemic stroke accounts for most stroke cases. Recently, microRNAs (miRNAs) have been verified to play critical roles in the development of stroke. Herein, we explored effects of miR-152-3p on vascular endothelial cell functions under hypoxia. Human umbilical vein endothelial cells (HUVECs) were treated with hypoxia to mimic cell injury in vitro. Reverse transcription quantitative polymerase chain reaction revealed that miR-152-3p exhibited high expression in HUVECs treated with hypoxia. The inhibition of miR-152-3p reversed hypoxia-induced decrease in cell viability and the increase in angiogenesis, according to the results of cell counting kit-8 assays and tube formation assays. miR-152-3p inhibition reversed the increase in endothelial cell permeability mediated by hypoxia, as shown by endothelial cell permeability in vitro assays. In addition, the increase in protein levels of angiogenetic markers and the decrease in levels of tight junction proteins induced by hypoxia were reversed by miR-152-3p inhibition. Mechanistically, miR-152-3p directly targets 3'-untranslated region of DEAD-box helicase 6 (DDX6), which was confirmed by luciferase reporter assays. DDX6 is lowly expressed in HUVECs under hypoxic condition, and mRNA expression and protein level of DDX6 were upregulated in HUVECs due to miR-152-3p inhibition. Rescue assays showed that DDX6 knockdown reversed effects of miR-152-3p on cell viability, angiogenesis and endothelial permeability. The results demonstrated that miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DDX6 under hypoxia.
Insights
MicroRNA-152-3p worsens vascular endothelial cell function during hypoxia by targeting DDX6. Inhibiting miR-152-3p improves cell viability, angiogenesis, and barrier integrity, offering potential therapeutic targets for ischemic stroke.
Area of Science:
- Biomedical Science
- Molecular Biology
- Cardiovascular Research
Background:
- Stroke, particularly ischemic stroke, is a leading global cause of death and disability.
- MicroRNAs (miRNAs) are increasingly recognized for their crucial roles in stroke pathogenesis.
- Understanding miRNA involvement in vascular endothelial cell (VEC) function under hypoxic conditions is vital for developing stroke therapies.
Purpose of the Study:
- To investigate the role of miR-152-3p in regulating VEC functions under hypoxia.
- To elucidate the molecular mechanism by which miR-152-3p affects VECs, focusing on its interaction with DEAD-box helicase 6 (DDX6).
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia to simulate in vitro injury.
- Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to measure miRNA and mRNA expression.
- Cell viability, angiogenesis, and endothelial permeability assays were performed.
- Luciferase reporter assays confirmed the direct targeting of DDX6 by miR-152-3p.
- Western blotting assessed protein levels of angiogenesis markers and tight junction proteins.
- Rescue assays involving DDX6 knockdown were conducted.
Main Results:
- Hypoxia significantly increased miR-152-3p expression in HUVECs.
- Inhibition of miR-152-3p improved cell viability, enhanced angiogenesis, and reduced endothelial permeability.
- miR-152-3p inhibition reversed hypoxia-induced changes in angiogenesis markers and tight junction proteins.
- miR-152-3p was confirmed to directly target DDX6, leading to decreased DDX6 expression under hypoxia.
- Upregulating DDX6 via miR-152-3p inhibition counteracted the detrimental effects on VECs.
Conclusions:
- miR-152-3p exacerbates VEC dysfunction under hypoxic conditions.
- The mechanism involves the direct targeting of DDX6 by miR-152-3p.
- Modulating miR-152-3p and its target DDX6 presents a potential therapeutic strategy for ischemic stroke.
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