Our previous study reported that
microRNA (miR)‑30a‑5p upregulation under
hypoxia postconditioning (HPostC) exert a protective effect on aged H9C2 cells against
hypoxia/reoxygenation injury via
DNA methyltransferase 3B‑induced
DNA hypomethylation at the miR‑30a‑5p gene promoter. This suggests that miR‑30a‑5p may be a potential preventative and therapeutic target for
ischemic heart disease in aged myocardium. The present study aimed to investigate the underlying mechanisms of miR‑30a‑5p transcription in aged myocardium in
ischemic heart disease. Cardiomyocytes were treated with 8 mg/ml D‑galactose for 9 days, and then exposed to hypoxic conditions. Cell viability was determined using a cell viability assay. Expression levels of
histone deacetylase 2 (HDAC2), LC3B‑II/I, beclin‑1 and p62 were detected via reverse transcription‑quantitative PCR and western blotting.
Chromatin immunoprecipitation‑PCR and
luciferase reporter assays were performed to evaluate the effect of c‑Myc binding and activity on the miR‑30a‑5p promoter in senescent cardiomyocytes following HPostC. It was found that HPostC enhanced the acetylation levels of H3K14 at the miR‑30a‑5p gene promoter in senescent cardiomyocytes, which attributed to the decreased expression of HDAC2. In addition, c‑Myc could positively regulate miR‑30a‑5p transcription to inhibit senescent cardiomyocyte autophagy. Mechanically, it was observed that increased H3K14 acetylation level exposed to
romidepsin facilitated c‑Myc binding to the miR‑30a‑5p gene promoter region, which led to the increased transcription of miR‑30a‑5p. Taken together, these results demonstrated that HDAC2‑mediated H3K14 hyperacetylation promoted c‑Myc binding to the miR‑30a‑5p gene promoter, which contributed to HPostC senescent cardioprotection.