MiR-339 is a potential biomarker of coronary heart disease to aggravate oxidative stress through Nrf2/FOXO3 targeting Sirt2

Background: MicroRNA (miRNA) is a class of small-molecule RNA that can regulate gene expression at post-transcription level. It is involved in the genesis and development of multiple diseases. The aim of this paper was to explore the mechanisms of miR-339 in coronary heart disease (CHD).

Methods: In this study, we enrolled patients with CHD from Beijing Chaoyang Hospital and performed animal experiments on CHD rats. In vitro experiments, such as histopathologic assay, quantitative real-time PCR assay, luciferase reporter assay, western blotting assay, and immunofluorescence assay were carried out to characterize the contents and associations of miR-339, Nrf2, FOXO3, and Sirt2 in CHD samples and cells. In vivo model was also established on rats.

Results: In CHD rat, miR-339 was up-regulated compared with control group. The expression of miR-339 up-regulation increased oxidative stress in vitro model via suppression of Sirt2/Nrf2/FOXO3. However, down-regulation of miR-339 expression inhibited oxidative stress in vitro model via activation of Sirt2/Nrf2/FOXO3. The Sirt2 or Nrf2 inhibitor reduced the protective effect of miR-339 down-regulation on oxidative stress in vitro model.

Conclusions: Down-regulation miR-339 may be the new targets to treat CHD through Nrf2/FOXO3 targeting Sirt2, and miR-339 may be a potential biomarker of CHD.