Research Paper Volume 13, Issue 18 pp 22444—22458
SUV39H2/KMT1B Inhibits the cardiomyocyte senescence phenotype by down-regulating BTG2/PC3
- 1 Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
- 2 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
Received: November 3, 2020 Accepted: August 24, 2021 Published: September 24, 2021
https://doi.org/10.18632/aging.203551How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Suppressor of variegation 3-9 homolog 2 (SUV39H2/KMT1B), a member of the SUV39 subfamily of lysine methyltransferases (KMTs), functions as an oncogene in various types of cancers. Here, we demonstrate a novel function of SUV39H2 that drives the cardiomyocyte aging process through BTG2. In our study, cardiomyocyte aging was induced by H2O2 and aging cells exhibited increases in SUV39H2. Knockdown of SUV39H2 accelerated cardiomyocyte senescence, while overexpression of SUV39H2 inhibited the cardiomyocyte senescence phenotype. These effects of SUV39H2 on cardiomyocytes were independent of DNA damage and mitochondrial dysfunction. Interestingly, RNA sequencing and bioinformatics analyses identified a strong correlation between SUV39H2 and BTG2. In addition to this, BTG2 protein levels were significantly increased in SUV39H2-deficient cardiomyocytes, and BTG2 knockdown virtually rescued the cardiomyocyte senescence phenotype induced by SUV39H2 knockdown. Taken together, these results indicate that SUV39H2 protects cardiomyocytes from H2O2 exposure-induced oxidative stress, DNA damage, and mitochondrial dysfunction by regulating the p53-BTG2 pathway. Our findings provide evidence that the activation of SUV39H2 has therapeutic or preventive potential against cardiac aging.
Abbreviations
ROS: reactive oxygen species; SUV39H2/KMT1B: The suppressor of variegation 3–9 homolog 2; KMTs: lysine methyltransferases; CVD: cardiovascular disease; H2O2: hydrogen peroxide; DCFH-DA: 2-dichlorofluorescein diacetate; RNA-seq: RNA sequencing; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; qPCR: Quantitative real time PCR.