Eur Rev Med Pharmacol Sci 2018; 22 (18): 6119-6126

DOI: 10.26355/eurrev_201809_15951

MiR-223 promotes cardiomyocyte apoptosis by inhibiting Foxo3a expression

P.-P. Wang, Y.-J. Zhang, T. Xie, J. Sun, X.-D. Wang

Department of Nursing, Medical College, Hebei University of Engineering, Handan, Hebei, China.wangpeipei19@126.com


OBJECTIVE: MicroRNAs (miRs) are proven to possess diversified functions in the pathogenesis of cardiac diseases. The current study is designed aiming at determining the effect of miR-223 on oxidative stress induced apoptosis in cardiomyocytes.

MATERIALS AND METHODS: Mouse model of myocardial infarction (MI) was constructed, and endogenous level of miR-223 in the border zone of infarcted heart tissues was determined. Primarily cultured cardiomyocytes were exposed to H2O2 treatment to mimic the oxidative stress stimulation. Multiple approaches including quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell viability assay, luciferase assay, Western blot assay and flow cytometry assay were employed to determine its expression, function and mechanism in apoptosis.

RESULTS: MiR-223 expression was significantly upregulated in the border zone of infarcted heart ventricular tissues and in cardiomyocytes treated with H2O2. Overexpression of miR-223 in cardiomyocytes promoted apoptosis, whereas inhibition of endogenous miR-223 protected cardiomyocytes from oxidative stress induced apoptosis. MiR-223 directly targets the 3’untranslated region (UTR) of Foxo3a mRNA. Overexpression of miR-223 inhibited Foxo3a protein expression, however, inhibition of miR-223 suppressed its expression. Silencing Foxo3a using small interfering RNA (siRNA) mimicked the effect of miR-223, indicating its functional significance.

CONCLUSIONS: MiR-223 is an important regulator of cardiomyocyte apoptosis under oxidative stress. Inhibition of the miR-223/Foxo3a signaling axis may be a potential therapeutic strategy for cardiac injuries.

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To cite this article

P.-P. Wang, Y.-J. Zhang, T. Xie, J. Sun, X.-D. Wang
MiR-223 promotes cardiomyocyte apoptosis by inhibiting Foxo3a expression

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 18
Pages: 6119-6126
DOI: 10.26355/eurrev_201809_15951