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Cardiovasc Drugs Ther · Dec 2019
LncRNA MALAT1 Promotes Oxygen-Glucose Deprivation and Reoxygenation Induced Cardiomyocytes Injury Through Sponging miR-20b to Enhance beclin1-Mediated Autophagy.
- Shuang Wang, Tao Yao, Fan Deng, Wenqian Yu, Yiting Song, Jingyi Chen, and Zhihua Ruan.
- Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.
- Cardiovasc Drugs Ther. 2019 Dec 1; 33 (6): 675-686.
Background/AimsLncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial I/R injury and closely related to autophagy. However, the exact biological role of MALAT1 and its underlying mechanism in myocardial I/R injury remain to be elucidated.MethodsWe established incultured H9C2 cardiomyocytes an oxygen-glucose deprivation and reoxygenation (OGD/R) model for 6 h and then reoxygen-glucose for 4 h. We measured cell damage and autophagy levels after OGD/R by real-time quantitative PCR and Western blot. The relationships between miR-20b and MALAT1, beclin1 were confirmed by luciferase reporter assay.ResultsWe found that the expression of MALAT1 and beclin1, cell damage levels (lactate dehydrogenase (LDH) release, 222.4 ± 29.4 vs. 577.5 ± 27.4 U/L; creatine kinase MB isoenzyme (CK-MB), 1.0 ± 0.2 vs. 4.3 ± 0.4; cardiac troponin I (cTn-I), 1.0 ± 0.3 vs. 3.0 ± 0.3; p < 0.05), and autophagy levels were significantly increased after OGD/R model, while cell viability (100.0 vs. 54.2 ± 2.2%, p < 0.05) and the expression of miR-20b and P62 were reduced; the trend of all the above data was significantly reversed by MALAT1 siRNA. In addition, the luciferase reporter assay results confirmed that MALAT1 directly binds to miR-20b-5p and functions as a ceRNA for miR-20b-5p to regulate beclin1. As a result, MALAT1 overexpression antagonized while MALAT1 knockdown enhanced the inhibitory effects of miR-20b-5p on beclin1-related cardiomyocytes autophagy in OGD/R injury.ConclusionLncRNA MALAT1 promotes OGD/R-induced cardiomyocytes injury through sponging miR-20b to enhance beclin1-mediated autophagy.
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