Journal
AGING-US
Volume 12, Issue 14, Pages 14365-14375Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103478
Keywords
circular RNA; circVEGFC; vascular endothelial cells; high glucose; VEGF
Categories
Funding
- National Nature Science Foundation of China [81760346]
- First Batch of High-level Talent Scientific Research Projects of the Affiliated Hospital of Youjiang Medical University for Nationalities in 2019 [R20196314]
- Guangxi Natural Science Foundation [2018GXNSFAA281148, 2019JJA140067]
- Scientific Research & Technology Development Program of Nanning [20183037-1, 20191034]
- Yong River Program of innovation and entrepreneurship of Nanning [2018-01-07]
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More and more findings illustrate the critical roles of circular RNA (circRNA) in diabetes mellitus (DM) and its complications. A major pathological characteristic for DM is the apoptosis of endothelial cells (ECs) induced by high glucose (HG), however, the function of circRNA in the ECs' phenotypes is still elusive. Here, this study identified an up-regulated circRNA (circVEGFC) in the HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of circVEGFC alleviated the apoptosis and recovered the proliferation in HUVECs induced by HG administration. Mechanistically, circVEGFC functioned as the sponge of miR-338-3p, and miR-338-3p was found to target the 3'-Untranslated Regions (3'-UTR) of hypoxia inducible factor 1 alpha (HIF-1 alpha). HIF-1 alpha, a critical transcription factor in DM, could activate the transcription of vascular endothelial growth factor A (VEGFA) and promote its protein product. In conclusion, these findings reveal the promotion of circVEGFC/miR-338-3p/HIF-1 alpha/VEGFA axis in the HG-induced ECs' apoptosis, providing a potential treatment strategy for ECs' damage in DM.
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