PMID- 33336750 OWN - NLM STAT- MEDLINE DCOM- 20210629 LR - 20210629 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 24 IP - 23 DP - 2020 Dec TI - MiR-204 reduces apoptosis in rats with myocardial infarction by targeting SIRT1/p53 signaling pathway. PG - 12306-12314 LID - 24023 [pii] LID - 10.26355/eurrev_202012_24023 [doi] AB - OBJECTIVE: The aim of this study was to investigate the influence of micro ribonucleic acid (miR)-204 on rats with myocardial infarction by targeting the silent information regulator 1 (SIRT1)/p53 signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: sham-operation group (n=12), model group (n=12) and miR-204 mimics group (n=12). The rats in the sham-operation group only underwent thoracotomy, without myocardial infarction injury. Meanwhile, the rats in model group and miR-204 mimics group were utilized to establish the models of myocardial infarction, and then, intervened with normal saline and miR-204 mimics, respectively. The morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining. Immunofluorescence was performed to detect the expression of Caspase-3. Target genes of miR-204 were analyzed using bioanalysis software. Western blotting (WB) assay was applied to measure the relative protein expression of SIRT1. MiR-204 expression and the messenger RNA (mRNA) expressions of SIRT1 and p53 were measured via quantitative Polymerase Chain Reaction (qPCR). Furthermore, cell apoptosis was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: HE staining showed that the morphology of myocardial tissues was normal in sham-operation group. Severe myocardial tissue injury was visible in model group, and the injury was relieved in miR-204 mimics group when compared with model group. The results manifested that the positive expression of Caspase-3 in cardiac tissues increased remarkably in the model group and miR-204 mimics group in comparison with sham-operation group (p<0.05). Meanwhile, it was evidently lower in miR-204 mimics group than model group (p<0.05). Based on the analysis via bioanalysis software, SIRT1 was the target gene of miR-204. WB results revealed that the relative protein expression level of SIRT1 was elevated notably in the other two groups compared with the 2sham-operation group (p<0.05). However, it was markedly lowered in miR-204 mimics group in contrast with model group (p<0.05). QRT-PCR results demonstrated that the model group and miR-204 mimics group exhibited distinctly lower expression of miR-204 but higher mRNA expressions of SIRT1 and p53 than sham-operation group (p<0.05). However, miR-204 mimics group exhibited prominently higher expression of miR-204 but lower mRNA expressions of SIRT1 and p53 than model group (p<0.05). Finally, the results of TUNEL assay demonstrated that the apoptosis rate increased remarkably in the model group and miR-204 mimics group when compared with sham-operation group (p<0.05). However, it decreased notably in miR-204 mimics group in comparison with model group (p<0.05). CONCLUSIONS: MiR-204 reduces the apoptosis level in rats with myocardial infarction via targeted inhibition of the SIRT1/p53 signaling pathway. FAU - Wang, L-Z AU - Wang LZ AD - Department of Cardiac, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China. urologistliu@hotmail.com. FAU - Xi, J-N AU - Xi JN FAU - Liu, T-J AU - Liu TJ FAU - Zhang, Z-Y AU - Zhang ZY FAU - Zhang, P AU - Zhang P LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (MIRN204 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Tp53 protein, rat) RN - 0 (Tumor Suppressor Protein p53) RN - EC 3.5.1.- (Sirt1 protein, rat) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - Apoptosis MH - MicroRNAs/genetics/*metabolism MH - Myocardial Infarction/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Sirtuin 1/genetics/*metabolism MH - Tumor Suppressor Protein p53/genetics/*metabolism EDAT- 2020/12/19 06:00 MHDA- 2021/06/30 06:00 CRDT- 2020/12/18 08:37 PHST- 2020/12/18 08:37 [entrez] PHST- 2020/12/19 06:00 [pubmed] PHST- 2021/06/30 06:00 [medline] AID - 24023 [pii] AID - 10.26355/eurrev_202012_24023 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12306-12314. doi: 10.26355/eurrev_202012_24023.