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  • H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury.

H3K14 hyperacetylation‑mediated c‑Myc binding to the miR‑30a‑5p gene promoter under hypoxia postconditioning protects senescent cardiomyocytes from hypoxia/reoxygenation injury.

Molecular medicine reports (2021-04-22)
Lingbo Xu, Huiping Zhang, Yanhua Wang, Wei Guo, Lingyu Gu, Anning Yang, Shengchao Ma, Yong Yang, Kai Wu, Yideng Jiang
ABSTRACT

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.

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Roche
Cell Viability Imaging Kit 5x96