METTL3 improves cardiomyocyte proliferation upon myocardial infarction via upregulating miR-17-3p in a DGCR8-dependent manner

Kun Zhao, Chuanxi Yang, Jing Zhang, Wei Sun, Bin Zhou, Xiangqing Kong, Jing Shi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Myocardial infarction (MI), one of the most severe types of heart attack, exerts a strong negative effect on heart muscle by causing a massive and rapid loss of cardiomyocytes. However, the existing therapies do little to improve cardiac regeneration. Due to the role of methyltransferase-like 3 (METTL3) in the physiological proliferation of cardiomyocytes, we aimed to determine whether METTL3 could also promote cardiomyocyte proliferation under pathological conditions and to elucidate the underlying mechanism. The effects of METTL3 on cardiomyocyte proliferation and apoptosis were investigated in an in vivo rat model of MI and in an in vitro model of neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia. We found that METTL3 expression was downregulated in hypoxia-exposed NRCMs and MI-induced rats. Furthermore, METTL3 pretreatment enhanced cardiomyocyte proliferation and inhibited cardiomyocyte apoptosis under hypoxic or MI conditions, and silencing METTL3 had the opposite effects. Additionally, METTL3 overexpression upregulated miR-17-3p expression. The miR-17-3p agomir mimicked the pro-proliferative and antiapoptotic effects of METTL3 in hypoxia-exposed cells or rats with MI, while the miR-17-3p antagomir blocked these effects. Additionally, pretreatment with the RNA-binding protein DGCR8 also hampered the protective role of METTL3 in hypoxia-exposed cells. Overall, the current study indicated that METTL3 could improve cardiomyocyte proliferation and subsequently ameliorate MI in rats by upregulating proliferation-related miR-17-3p in a DGCR8-dependent pri-miRNA-processing manner.

Original languageEnglish (US)
Article number291
JournalCell Death Discovery
Issue number1
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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