Scholarlink

Background <p>Post-infarction myocardial fibrosis is a pivotal pathological process leading to heart failure; however, its epitranscriptional regulatory mechanisms remain poorly defined. The role of the MYC-METTL1-HILPDA axis in this process remains unexplored.</p> Methods <p>Myocardial infarction (MI) models were established in mice, and hypoxia-induced mouse cardiac fibroblasts were used. A range of molecular techniques, including qRT-PCR, Western blot, immunohistochemistry, RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays, were employed to investigate the MYC-METTL1-HILPDA axis.</p> Results <p>Following MI, METTL1 and HILPDA were significantly upregulated in cardiac tissue. METTL1 stabilized HILPDA mRNA via m7G modification, thereby enhancing its protein expression. Functional studies demonstrated that HILPDA overexpression induced mitochondrial dysfunction and fibroblast activation, whereas HILPDA knockdown attenuated these effects. Furthermore, the transcription factor MYC was identified as an upstream regulator that directly binds the METTL1 promoter to activate its transcription. Crucially, HILPDA knockdown improved cardiac function, attenuated fibrosis, and reduced infarct size in mice.</p> Conclusion <p>This study identifies the MYC-METTL1-HILPDA axis as a novel driver of post-infarction myocardial fibrosis, which promotes mitochondrial dysfunction and fibroblast activation through m7G-mediated stabilization of HILPDA mRNA. These findings provide new mechanistic insights and reveal potential therapeutic targets for preventing heart failure.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

MYC promotes myocardial fibrosis via METTL1-mediated m7G modification of HILPDA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月11日

查看全文
  • Yue Liu,
  • Kai Li,
  • Yi Chen,
  • Huasong Xia

摘要

Background

Post-infarction myocardial fibrosis is a pivotal pathological process leading to heart failure; however, its epitranscriptional regulatory mechanisms remain poorly defined. The role of the MYC-METTL1-HILPDA axis in this process remains unexplored.

Methods

Myocardial infarction (MI) models were established in mice, and hypoxia-induced mouse cardiac fibroblasts were used. A range of molecular techniques, including qRT-PCR, Western blot, immunohistochemistry, RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays, were employed to investigate the MYC-METTL1-HILPDA axis.

Results

Following MI, METTL1 and HILPDA were significantly upregulated in cardiac tissue. METTL1 stabilized HILPDA mRNA via m7G modification, thereby enhancing its protein expression. Functional studies demonstrated that HILPDA overexpression induced mitochondrial dysfunction and fibroblast activation, whereas HILPDA knockdown attenuated these effects. Furthermore, the transcription factor MYC was identified as an upstream regulator that directly binds the METTL1 promoter to activate its transcription. Crucially, HILPDA knockdown improved cardiac function, attenuated fibrosis, and reduced infarct size in mice.

Conclusion

This study identifies the MYC-METTL1-HILPDA axis as a novel driver of post-infarction myocardial fibrosis, which promotes mitochondrial dysfunction and fibroblast activation through m7G-mediated stabilization of HILPDA mRNA. These findings provide new mechanistic insights and reveal potential therapeutic targets for preventing heart failure.

Graphical Abstract