ZNFX1 suppresses apoptosis-associated mRNA stability in cardiomyocyte to protect against myocardial infarction

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Cell Death Mechanisms

Background:

• Cardiovascular diseases, particularly myocardial infarction (MI), represent a significant global health challenge.
• The role of Zinc finger NFX1-type containing 1 (ZNFX1), an RNA helicase, in cardiovascular pathologies is largely unexplored.

Purpose of the Study:

• To investigate the involvement and underlying mechanisms of ZNFX1 in myocardial infarction.
• To determine the therapeutic potential of ZNFX1 in cardiovascular disease.

Main Methods:

• Quantitative analysis of ZNFX1 expression in MI models and hypoxia-treated cardiomyocytes.
• In vivo studies involving ZNFX1 overexpression and knockdown in mouse models of MI.
• RNA sequencing (RNA-seq) to identify ZNFX1-regulated pathways, focusing on apoptosis.
• Analysis of ZNFX1's role in degrading mRNA of apoptosis-related genes with structured 3'UTRs.

Main Results:

• ZNFX1 expression was found to be decreased in MI myocardium and hypoxia-induced cardiomyocytes.
• Overexpression of ZNFX1 attenuated myocardial dysfunction, reduced infarct size, and alleviated cardiac hypertrophy and collagen deposition in MI mice.
• Knockdown of ZNFX1 exacerbated MI phenotypes.
• ZNFX1 was identified to repress cardiomyocyte apoptosis, a key factor in MI development, by degrading specific mRNAs.

Conclusions:

• ZNFX1 plays a crucial protective role in myocardial infarction by regulating programmed cell death.
• ZNFX1 achieves this protection through the degradation of apoptosis-related gene messenger RNAs (mRNAs) possessing structured 3' untranslated regions (3'UTRs).
• This research highlights ZNFX1 as a potential novel therapeutic target for cardiovascular diseases and other conditions characterized by critical apoptosis pathways.