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

Cardiovascular diseases remain a growing global health burden, with myocardial infarction (MI) persisting as the leading cause of cardiovascular mortality worldwide. Zinc finger NFX1-type containing 1 (ZNFX1), an RNA helicase family member, remains relatively understudied in molecular biology and its role in cardiovascular diseases remains unclear. This study aims to explore the involvement of ZNFX1 in MI and uncover its mechanisms. This research found ZNFX1 was decreased in MI myocardium and hypoxia-treated cardiomyocyte. Overexpression of ZNFX1 significantly attenuated myocardial dysfunction, reduced infarct size, inhibited collagen deposition and alleviated cardiac hypertrophy which was ascribed to MI in mice, whereas knockdown of ZNFX1 produced the opposite effects. Mechanistically, RNA-seq identified apoptosis as a possible regulated pathway of ZNFX1, overexpression of ZNFX1 repressed the cardiomyocyte apoptosis that gives rise to MI while knockdown of ZNFX1 deteriorated it. Given the structural similarity between ZNFX1 and UPF1 that confers RNA decay functionality, an in-depth investigation is needed to understand the collective impact of ZNFX1-mediated RNA decay on the process of apoptosis. Here, we report that ZNFX1 plays a protective role in MI by degrading mRNA of apoptosis-related genes, which possess highly structured 3'UTRs. Collectively, this study provides a novel insight into the regulatory mechanisms of programmed cell death, potentially uncovering new targets for therapeutic intervention in diseases where apoptosis is a critical factor.