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FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt

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Abstract

Heart failure (HF) is the end stage of many cardiovascular diseases and seriously threatens people’s health. This article aimed to explore the biological role of fat-mass and obesity-associated gene (FTO) in HF. We constructed HF mouse model by transverse aortic constriction or intraperitoneal injection of doxorubicin. Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. HF mice exhibited an increase in the total levels of N6 methyladenosine (m6A) and the m6A levels of Mhrt. Moreover, FTO overexpression caused an upregulation of Mhrt and reduced m6A modification of Mhrt in the H/R-treated myocardial cells. FTO upregulation repressed apoptosis of H/R-treated myocardial cells. FTO knockdown had the opposite results. Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. Moreover, the influence conferred by FTO upregulation was abolished by Mhrt knockdown. In conclusion, our data demonstrate that FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Thus, FTO may be a target gene for HF treatment.

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Funding

This study was approved by The special projects of development in local science and technology guided by the central government (2016080802D113); Natural Science Foundation of Anhui Province (1808085MH281); and New Medicine of University of Science and Technology of China (WK9110000046).

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Authors and Affiliations

  1. Department of Cardiovascular, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No.17 Lujiang Road, Hefei, 230001, China

    Wei Shen, Hao Su, Kangyu Chen & Ji Yan

  2. Department of Gerontology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China

    Hongqi Li

Authors
  1. Wei Shen
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  2. Hongqi Li
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  3. Hao Su
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  4. Kangyu Chen
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  5. Ji Yan
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Contributions

WS designed the study. All authors participated in the experiments and contributed to the data analysis. WS drafted the paper. All authors approved the paper.

Corresponding author

Correspondence to Ji Yan.

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The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Ethics Committee of The First Affiliated Hospital of USTC.

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11010_2021_4069_MOESM1_ESM.tif

Myocardial cells were transfected with OE-Mhrt or pcDNA3.1-NC, and then exposed to H/R. Myocardial cells exposed to normal oxygen as control. The apoptosis of the myocardial cells was estimated by flow cytometry. &P < 0.05 vs. Control; *P < 0.05 vs. Vector; #P < 0.05 vs. shCtrl (TIF 691 kb)

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Shen, W., Li, H., Su, H. et al. FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Mol Cell Biochem 476, 2171–2179 (2021). https://doi.org/10.1007/s11010-021-04069-6

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  • DOI: https://doi.org/10.1007/s11010-021-04069-6

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