MicroRNA‑26a protects vascular smooth muscle cells against H2O2‑induced injury through activation of the PTEN/AKT/mTOR pathway

Peng,Junlu; He,Xinqi; Zhang,Lei; Liu,Peng

doi:10.3892/ijmm.2018.3746

MicroRNA‑26a protects vascular smooth muscle cells against H2O2‑induced injury through activation of the PTEN/AKT/mTOR pathway

Authors:
- Junlu Peng
- Xinqi He
- Lei Zhang
- Peng Liu
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Affiliations: Department of Vascular Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: June 27, 2018 https://doi.org/10.3892/ijmm.2018.3746
Pages: 1367-1378
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abdominal aortic aneurysm (AAA) is a common disease, which is characterized by the apoptosis of vascular smooth muscle cells (VSMCs). In previous years, microRNAs (miRNAs) have been associated with AAA and functionally implicated in the pathogenesis of this disease. However, the role of miRNAs in the apoptosis of VSMCs remains to be fully elucidated. The present study aimed to elucidate the role and mechanism of miRNAs in protecting against hydrogen peroxide (H2O2)‑induced apoptosis in VSMCs. The expression of miRNAs in peripheral blood from patients diagnosed with AAA was analyzed using a microarray and reverse transcription polymerase chain reaction. A VSMC injury model induced by H2O2 was used to determine the potential role of miR‑26a against cell injury. Cell viability, cell apoptosis and reactive oxygen species (ROS) generation were determined by a CCK8 assay, flow cytometry and a 2',7'‑DCF diacetate assay, respectively. It was observed that miRNA (miR)‑26a (miR‑26a‑1‑5p) was significantly downregulated in peripheral blood samples from patients with AAA. It was revealed that H2O2 treatment dose‑dependently inhibited cell viability, enhanced apoptosis and induced the production of ROS, which indicated the success of the model establishment. It was also observed that miR‑26a was downregulated in the VSMCs following H2O2 stimulation. The upregulation of miR‑26a attenuated H2O2‑induced cell injury, as evidenced by the enhancement of cell viability, and inhibition of the activity of caspase‑3, apoptosis and ROS production. In addition, phosphatase and tensin homolog (PTEN), a well‑known regulator of the AKT/mammalian target of rapamycin (mTOR) pathway, was found to be a direct target of miR‑26a in the VSMCs and this was validated using a luciferase reporter assay. Overexpression of PTEN by pcDNA‑PTEN plasmids markedly eliminated the protective effects of the overexpression of miR‑26a on H2O2‑induced cell injury. Finally, it was found that miR‑26a mediated its anti‑apoptotic action by reactivation of the AKT/mTOR pathway, as demonstrated by the upregulation of phosphorylated (p‑)AKT and p‑mTOR, and the Akt inhibitor API‑2 reversing the protective effects on VSMCs mediated by miR‑26a. These results indicated that miR‑26a protected VSMCs against H2O2‑induced injury through activation of the PTEN/AKT/mTOR pathway, and miR‑26a may be considered as a potential prognostic biomarker and therapeutic target in the treatment of AAA.

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