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Updated: Oct 20, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Overexpression of hsa_circ_0022742 suppressed hyperglycemia-induced endothelial dysfunction by targeting the
Siyang Liu1, Liyun Wang1, Xueyan Wu2
1Chengde Central Hospital, Chengde, Hebei 067000, China.
Insights
High glucose levels in diabetes damage blood vessels. This study shows that increasing hsa_circ_0022742 can protect against this damage by regulating the miR-503-5p/FBXW7 pathway.
Area of Science:
- Endocrinology
- Molecular Biology
- Vascular Biology
Background:
- Diabetes mellitus (Type I and II) negatively impacts organ microvasculature.
- Hyperglycemia (HG)-induced endothelial dysfunction is linked to altered circular RNA (circRNA) expression.
- The precise regulatory mechanisms underlying these effects remain incompletely understood.
Purpose of the Study:
- To investigate the role of circRNAs in hyperglycemia-induced endothelial dysfunction.
- To elucidate the molecular mechanism of hsa_circ_0022742 in protecting against HG-induced endothelial damage.
- To identify downstream targets of hsa_circ_0022742.
Main Methods:
- High-throughput sequencing of circRNAs in human umbilical vein endothelial cells (HUVECs) under HG conditions.
- Bioinformatics analysis, luciferase reporter assays, and qRT-PCR to validate molecular interactions.
- Flow cytometry and angiogenic differentiation assays to assess endothelial cell function.
Main Results:
- HG treatment decreased hsa_circ_0022742 expression in HUVECs.
- Overexpression of hsa_circ_0022742 ameliorated HG-induced endothelial dysfunction, including reduced apoptosis and inflammation.
- hsa_circ_0022742 targets miR-503-5p and FBXW7, enhancing FBXW7 expression by sponging miR-503-5p.
Conclusions:
- hsa_circ_0022742 plays a protective role against hyperglycemia-induced endothelial dysfunction.
- The miR-503-5p/FBXW7 axis is a key downstream pathway regulated by hsa_circ_0022742.
- Targeting the hsa_circ_0022742/miR-503-5p/FBXW7 pathway may offer therapeutic potential for diabetic microvascular complications.
Abstract:
Type I and II diabetes adversely affect the microvasculature of several organs, although the regulatory mechanisms remain unclear. Previous studies have found that differentially expressed circRNAs associated with hyperglycemia (HG) induce endothelial dysfunction. In the present study, high-throughput sequencing was employed to assess abnormal circRNA expression in human umbilical vein endothelial cells (HUVECs) after HG treatment. Then, bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation analysis, flow cytometry, and qRT-PCR analysis were performed to investigate the underlying regulatory mechanism and targets. The results demonstrate that hsa_circ_0022742 expression in HUVECs was decreased by HG treatment and overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction. Luciferase analysis showed that miR-503-5p and FBXW7 were downstream targets of hsa_circ_0022742. Both overexpression of FBXW7 and inhibition of miR-503-5p reversed the protective effect of hsa_circ_0022742 against HG-induced endothelial dysfunction, including apoptosis, abnormal vascular differentiation, and secretion of inflammatory factors, indicating that hsa_circ_0022742 enhanced FBXW7 expression by sponging miR-503-5p. Taken together, these findings demonstrate that overexpression of hsa_circ_0022742 suppressed HG-induced endothelial dysfunction by targeting the miR-503-5p/FBXW7 axis.
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