Downregulation of lncRNA MIR181A2HG by high glucose impairs vascular endothelial cell proliferation and migration through the dysregulation of the miRNAs/AKT2 axis

Wang,Shaohua; Wang,Shaohua; Zheng,Bin; Zheng,Bin; Zhao,Hongye; Zhao,Hongye; Li,Yongjun; Li,Yongjun; Zhang,Xinhua; Zhang,Xinhua; Wen,Jinkun; Wen,Jinkun

doi:10.3892/ijmm.2021.4868

Downregulation of lncRNA MIR181A2HG by high glucose impairs vascular endothelial cell proliferation and migration through the dysregulation of the miRNAs/AKT2 axis

Authors:
- Shaohua Wang
- Bin Zheng
- Hongye Zhao
- Yongjun Li
- Xinhua Zhang
- Jinkun Wen
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Affiliations: Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Clinical Laboratorial Examination, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. Chin
Published online on: February 2, 2021 https://doi.org/10.3892/ijmm.2021.4868
Article Number: 35
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endothelial dysfunction and diabetic vascular disease induced by chronic hyperglycemia involve complex interactions among high glucose, long non‑coding RNAs (lncRNAs), microRNAs (miRNAs or miRs) and the Ser/Thr kinase AKT. However, the molecular mechanisms underlying the regulatory crosstalk between these have not yet been completely elucidated. Thus, the present study aimed to explore the molecular mechanisms whereby high glucose (HG)‑induced lncRNA MIR181A2HG modulates human umbilical vein endothelial cell (HUVEC) proliferation and migration by regulating AKT2 expression. The persistent exposure of HUVECs to HG resulted in MIR181A2HG downregulation and thus reduced its ability to sponge miR‑6832‑5p, miR‑6842‑5p and miR‑8056, subsequently leading to an increase in miR‑6832‑5p, miR‑6842‑5p and miR‑8056 levels. Mechanistically, miR‑6832‑5p, miR‑6842‑5p and miR‑8056 were found to target the 3'UTR of AKT2 mRNA in HUVECs, and the increase in their levels led to a decreased expression of AKT2. Thus, this also led to the suppression of HUVEC proliferation and migration, and the formation of capillary‑like structures. Moreover, the suppression of HUVEC proliferation and migration induced by MIR181A2HG downregulation was accompanied by changes in glucose metabolism. On the whole, the present study demonstrates that the downregulation of lncRNA MIR181A2HG by HG impairs HUVEC proliferation and migration by dysregulating the miRNA/AKT2 axis. The MIR181A2HG/miRNA/AKT2 regulatory axis may thus be a potential therapeutic target for HG‑induced endothelial dysfunction.

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