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LncRNA MALAT1 Promotes Oxygen-Glucose Deprivation and Reoxygenation Induced Cardiomyocytes Injury Through Sponging miR-20b to Enhance beclin1-Mediated Autophagy

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Abstract

Background/Aims

LncRNA 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.

Methods

We 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.

Results

We 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.

Conclusion

LncRNA MALAT1 promotes OGD/R-induced cardiomyocytes injury through sponging miR-20b to enhance beclin1-mediated autophagy.

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Funding

This study was supported by Taihe Hospital Science and Technology Project in 2018 to Dr. Chen, Jingyi (grant numbers 2018JJXM046).

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Author notes

  1. Shuang Wang and Tao Yao contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China

    Shuang Wang, Wenqian Yu, Jingyi Chen & Zhihua Ruan

  2. Dongfeng General Hospital, Hubei University of Medicine, Shiyan, 442000, China

    Shuang Wang

  3. Department of Anesthesiology, Shenzhen Bao’an Maternity and Child Health Hospital, Shenzhen, 518100, China

    Tao Yao & Yiting Song

  4. Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Fan Deng

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  1. Shuang Wang
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  2. Tao Yao
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Contributions

Shuang Wang, Tao Yao, and Zhihua Ruan conceived and designed the project. Shuang Wang and Tao Yao performed the experiments with the help of Fan Deng, Wenqian Yu, Yiting Song, and Jingyi Chen. Fan Deng and Shuang Wang analyzed the data. Shuang Wang wrote the manuscript. All authors discussed the manuscript.

Corresponding authors

Correspondence to Yiting Song, Jingyi Chen or Zhihua Ruan.

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Wang, S., Yao, T., Deng, F. et al. LncRNA MALAT1 Promotes Oxygen-Glucose Deprivation and Reoxygenation Induced Cardiomyocytes Injury Through Sponging miR-20b to Enhance beclin1-Mediated Autophagy. Cardiovasc Drugs Ther 33, 675–686 (2019). https://doi.org/10.1007/s10557-019-06902-z

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  • DOI: https://doi.org/10.1007/s10557-019-06902-z

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