Myocardial infarction (MI) is pathologically characterized by the prolonged ischemic-induced death of cardiomyocytes.1 Acute MI triggers physiological responses such as increased heart rate, blood pressure, pulse wave, myocardial contractility, and oxygen demand, leading to coronary vasoconstriction and hypercoagulability.2 Current therapeutic approaches for MI are limited and non-curative, necessitating a deeper understanding of the molecular mechanism associated with MI for more effective treatment.3

MicroRNA (miR), a class of RNA molecules, play a pivotal role in the post-MI cellular responses, influencing cardiac function in a cell-type-specific manner.4 Various miRs, such as miR-21 and miR-133, have demonstrated therapeutic potential in modulating cardiac function post-MI.5,6 While miR-322 has been implicated in plaque instability in atherosclerosis,7 its involvement in MI, particularly through miR-322-5p, remains incompletely understood. Notably, miR-322-5p has been associated with angiogenesis in MI and demonstrated protective effects against ischemia-reperfusion injury.8,9,10 However, the specific mechanisms linking miR-322-5p to MI are yet to be elucidated.

Our study, guided by predictions from the TargetScan website, identifies a binding site between miR-322-5p and B-cell translocation gene 2 (BTG2), emphasizing their potential association. BTG2, part of the BTG/TOB gene family, is known for its regulatory roles in cardiac physiology. T-box 20 (Tbx20)-mediated suppression of BTG2 induces neonatal cardiomyocyte proliferation, while overexpressed BTG2 represses cardiomyocyte survival under hypoxic conditions.11,12 “BTG2 has been shown to be post-transcriptionally regulated by miR-21 to protect cardiomyocytes from doxorubicin-induced injury.13

In light of these references, our study highlights the regulatory mechanism of the miR-322-5p/BTG2 axis. We hypothesize that miR-322-5p, through suppressing BTG2 expression, plays a protective role against MI. This research contributes to a deeper understanding of the molecular intricacies underlying MI and presents a potential avenue for therapeutic intervention.