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Updated: Jun 18, 2026
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNA-300-3p promotes cardiac hypertrophy by modulating the ACOX-1/GPX4 pathway
Xiaojuan Li1, Yanjia Wang2, Ziyao Yang3
1Department of Critical Care Medicine, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.
Insights
MicroRNAs regulate cardiac hypertrophy (CH) by targeting ACOX1, promoting ferroptosis. DNMT1-mediated hypomethylation of miR-300-3p enhances this process, revealing a novel pathway for CH therapeutics.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Epigenetics
Background:
- Cardiac hypertrophy (CH) is a critical factor in heart failure development.
- MicroRNAs (miRNAs) are implicated in cardiovascular diseases, but their role in CH requires further elucidation.
- Understanding molecular mechanisms of CH is vital for therapeutic advancements.
Purpose of the Study:
- To investigate the role of miR-300-3p in angiotensin II (Ang II)-induced cardiac hypertrophy.
- To identify the molecular targets and pathways regulated by miR-300-3p in CH.
- To explore the epigenetic regulation of miR-300-3p in the context of CH.
Main Methods:
- In vitro studies using cell models of Ang II-induced CH.
- Analysis of miR-300-3p targeting of ACOX1 using luciferase assays and Western blotting.
- Assessment of ferroptosis markers and cell viability.
- Investigation of DNMT1-mediated promoter methylation of miR-300-3p.
- In vivo validation of the miR-300-3p/ACOX1/GPX4 axis.
Main Results:
- miR-300-3p directly targets and downregulates ACOX1, promoting ferroptosis in Ang II-induced CH.
- Overexpression of ACOX1 counteracted the effects of miR-300-3p, reducing ferroptosis and hypertrophy.
- DNMT1-mediated hypomethylation of the miR-300-3p promoter increased its expression, contributing to CH.
- ACOX1 demonstrated anti-hypertrophic effects through the GPX4 signaling pathway.
Conclusions:
- DNMT1-regulated promoter hypomethylation enhances miR-300-3p expression, which suppresses ACOX1 and promotes ferroptosis in Ang II-induced CH.
- The identified miR-300-3p/ACOX1/GPX4 signaling axis provides novel molecular insights into CH.
- This pathway represents a potential therapeutic target for managing CH and preventing heart failure progression.
Abstract:
Cardiac hypertrophy (CH) represents a key pathological process in cardiac remodeling and progression toward heart failure. Understanding its underlying molecular mechanisms is essential for developing novel therapeutic strategies. MicroRNAs (miRNAs) play crucial regulatory roles in cardiovascular diseases, however, their specific involvement in CH remains incompletely understood. Here, we demonstrate that miR-300-3p modulates angiotensin II (Ang II)-induced CH through the ACOX1/GPX4 pathway. Functionally, miR-300-3p directly targets ACOX1, leading to its downregulation and subsequent enhancement of ferroptosis. Overexpression of ACOX1 reversed these effects. Mechanistically, hypomethylation of the miR-300-3p promoter region, mediated by DNMT1, elevated miR-300-3p expression and contributed to Ang II-induced hypertrophic responses. Furthermore, ACOX1 exerted anti-hypertrophic effects via activation of the GPX4 signaling pathway. In conclusion, DNMT1-regulated promoter hypomethylation enhances miR-300-3p expression, suppresses ACOX1, and promotes ferroptosis in Ang II-induced CH. The miR-300-3p/ACOX1/GPX4 axis uncovers novel molecular pathways in CH and identifies potential therapeutic regulators.
