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

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.

The role of microRNAs in the involvement of vascular smooth muscle cells in the development of atherosclerosis

“…The Akt inhibitor API‐2 can reverse the anti‐apoptotic effect of miR‐26a on VSMCs, thereby having a protective effect on VSMCs. Together, these results indicated that miR‐26a protected VSMCs from H 2 O 2 ‐induced damage by activating the PTEN/AKT/mTOR pathway (Peng et al, ). SMAD1 and SMAD4 are two TGF‐β and BMP‐associated differentiation‐promoting factors, and overexpression of miR‐26a inhibited VSMCs differentiation and helped maintain cell balance in both synthetic and contractile states.…”

“…Thus, it was confirmed that miR‐26a had a regulatory effect on PDGF‐BB‐mediated Smad1 expression in VSMCs. Peng et al () show that miR‐26a expression was down‐regulated in VSMCs after H 2 O 2 stimulation. However, up‐regulation of miR‐26a attenuated H 2 O 2 ‐induced cell damage by enhancing cell viability, and inhibiting caspase‐3 activity, apoptosis, and reactive oxygen species production.…”

Sperm miR‐26a‐5p and its target PTEN transcripts content in men with unexplained infertility

“…Kang et al 16 and Peng et al 17 demonstrated that miR‐26a‐5p has protective effects against H 2 O 2 ‐induced cytotoxicity and apoptosis in vascular smooth muscle and RGC‐5 cells through downregulation of PTEN. Moreover, the anti‐apoptotic and pro‐survival potential of miR‐26a‐5p by targeting PTEN gene has been reported in sperm cells 18 .…”

“…MiR‐26a‐5p is a small non‐coding RNA that has activation effect on cell proliferation and apoptosis with activation of PI3K/AKT signaling pathway via targeting phosphatase and tensin homolog gene (PTEN) 15 . It has been shown that miR‐26a‐5p protects vascular smooth muscle and RGC‐5 cells against H 2 O 2 ‐induced cytotoxicity and apoptosis through downregulation of PTEN 16,17 . Ma et al 18 reported the association of sperm quality and motility with miR‐26a‐5p by targeting PTEN 18 .…”

Resveratrol Suppresses Ovarian Cancer Cell Growth and Invasion Through Upregulation of microRNA-34a

“…The samples were assessed using the miRCURY LNA™ Array v. 18.0 (Agilent). The procedure and imaging processes were as described previously (Peng et al 2018).…”