Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes 
mellitus, which can result in cardiac hypertrophy and subsequent heart failure, 
associated with pyroptosis, the pro-inflammatory programmed cell death. 
MicroRNAs (miRNAs), small endogenous non-coding RNAs, have been shown to be 
involved in diabetic cardiomyopathy. However, whether miRNAs regulate pyroptosis 
in diabetic cardiomyopathy remains unknown. Our study revealed that mir-30d 
expression was substantially increased in streptozotocin (STZ)-induced diabetic 
rats and in high-glucose-treated cardiomyocytes as well. Upregulation of mir-30d 
promoted cardiomyocyte pyroptosis in diabetic cardiomyopathy; conversely, 
knockdown of mir-30d attenuated it. In an effort to understand the signaling 
mechanisms underlying the pro-pyroptotic property of mir-30d, we found that 
forced expression of mir-30d upregulated caspase-1 and pro-inflammatory 
cytokines IL-1β and IL-18. Moreover, mir-30d directly repressed foxo3a 
expression and its downstream protein, apoptosis repressor with caspase 
recruitment domain (ARC). Furthermore, silencing ARC by siRNA mimicked the 
action of mir-30d: upregulating caspase-1 and inducing pyroptosis. These 
findings promoted us to propose a new signaling pathway leading to cardiomyocyte 
pyroptosis under hyperglycemic conditions: mir-30d↑→foxo3a↓→ 
ARC↓→caspase-1↑→IL-1β, IL-18↑→pyroptosis↑. Therefore, mir-30d may be a promising 
therapeutic target for the management of diabetic cardiomyopathy.