Hao Hu1, Jiawei Wu1, Dan Li1, Junling Zhou1, Hua Yu1, Likun Ma2. 1. Department of Cardiovascular, The First Affiliated Hospital of USTC, Hefei 230001, Anhui, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China. 2. Department of Cardiovascular, The First Affiliated Hospital of USTC, Hefei 230001, Anhui, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China. Electronic address: likunma633@yeah.net.
Abstract
BACKGROUND: Long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development of acute myocardial infarction (AMI). However, the molecular mechanism and biological function of MALAT1 in AMI remained unclear. METHODS: The expression levels of MALAT1, miR-320 and phosphatase and tensin homolog deleted on chromosome 10 (Pten) in a mouse model of AMI and sham-operated mice were determined by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. The relationships between miR-320 and MALAT1, Pten were confirmed by luciferase reporter assay. The roles of MALAT1, miR-320 and Pten in myocardial apoptosis were evaluated using Annexin V-FITC/PI double-labeled flow cytometry. Echocardiographic evaluation, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarct size and myocardial apoptosis using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were used to examine the impact of MALAT1 on myocardial injury. RESULTS: MALAT1 and Pten were highly expressed, while miR-320 was suppressed in MI group. Mechanistically, MALAT1 may serve as a sponge for miR-320 to upregulate Pten, a direct target of miR-320. Moreover, MALAT1 knockdown overturned the pro-apoptotic effect of miR-320 in vitro and in vivo. CONCLUSION: MALAT1 knockdown attenuated myocardial apoptosis through suppressing Pten expression by sponging miR-320 in mouse AMI.
BACKGROUND: Long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development of acute myocardial infarction (AMI). However, the molecular mechanism and biological function of MALAT1 in AMI remained unclear. METHODS: The expression levels of MALAT1, miR-320 and phosphatase and tensin homolog deleted on chromosome 10 (Pten) in a mouse model of AMI and sham-operated mice were determined by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. The relationships between miR-320 and MALAT1, Pten were confirmed by luciferase reporter assay. The roles of MALAT1, miR-320 and Pten in myocardial apoptosis were evaluated using Annexin V-FITC/PI double-labeled flow cytometry. Echocardiographic evaluation, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarct size and myocardial apoptosis using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were used to examine the impact of MALAT1 on myocardial injury. RESULTS:MALAT1 and Pten were highly expressed, while miR-320 was suppressed in MI group. Mechanistically, MALAT1 may serve as a sponge for miR-320 to upregulate Pten, a direct target of miR-320. Moreover, MALAT1 knockdown overturned the pro-apoptotic effect of miR-320 in vitro and in vivo. CONCLUSION:MALAT1 knockdown attenuated myocardial apoptosis through suppressing Pten expression by sponging miR-320 in mouse AMI.