Reduced DNMT1 levels induce cell apoptosis via upregulation of METTL3 in cardiac hypertrophy.

DNA methylation is also involved in the development and progression of cardiac diseases. Although studies have shown that DNA methylation and RNA m6A methylation play an important role in the development of myocardial hypertrophy, whether DNA methylation and RNA m6A methylation have a coordinated role in the development of myocardial hypertrophy and influence each other is still unknown. Here, we found that DNMT1 expression was downregulated in TAC mice and Ang II-treated NRCMs. Moreover, DNMT1 overexpression inhibited Ang II-induced apoptosis of NRCMs. Furthermore, we found that the expression of METTL3 was up-regulated after inhibiting the expression of DNMT1 by a DNMT1 inhibitor or small interfering RNA. In addition, ectopic expression DNMT1 inhibited METTL3 expression in NRCMs. Furthermore, METTL3 expression was elevated in NRCMs treated with Ang II, and suppression of METTL3 inhibited cell apoptosis induced by Ang II in NRCMs.In addition, this study revealed that the DNMT1/METTL3 pathway affected Ang II-induced apoptosis in NRCMs. Finally, this study found that DNMT1, but not METTL3, might directly regulated the ANP and BNP expression. Collectively, our findings revealed the role of the DNMT1/METTL3 pathway in cardiac hypertrophy and provided a novel molecular mechanism describing the physiological and pathological processes.