https://doi.org/10.4081/ejh.2022.3426

MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway

Vol. 66 No. 3 (2022)
Submitted: 20 April 2022
Accepted: 25 May 2022
Published: 21 June 2022
Hypertrophy, cardiomyocytes, MALAT1, miR-181a, HMGB2
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Authors

Feng Chen
Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong; Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi , China.
Wenfeng Li
Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong; Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi , China.
Dandan Zhang
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.
Youlin Fu
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.
Wenjin Yuan
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.
Gang Luo
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.
Fuwei Liu
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.
Jun Luo
luojun_1996@163.com
Department of Cardiology, Ganzhou People’s Hospital, Nanchang University, Ganzhou, Jiangxi, China.

Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between them during this process remain unknown. In the present study, we treated primary cardiomyocytes with angiotensin II (Ang II) to mimic cardiac hypertrophy. MALAT1 expression was significantly downregulated in Ang II-treated cardiomyocytes compared with control cardiomyocytes. Ang II-induced cardiac hypertrophy was suppressed by overexpression of MALAT1 and promoted by genetic knockdown of MALAT1. A dual-luciferase reporter assay demonstrated that MALAT1 acted as a sponge for miR-181a and inhibited its expression during cardiac hypertrophy. Cardiac hypertrophy was suppressed by overexpression of a miR-181a inhibitor and enhanced by overexpression of a miR-181a mimic. HMGB2 was downregulated during cardiac hypertrophy and was identified as a target of miR-181a by bioinformatics analysis and a dual-luciferase reporter assay. miR-181a overexpression decreased the mRNA and protein levels of HMGB2. Rescue experiments indicated that MALAT1 overexpression reversed the effect of miR-181a on HMGB2 expression. In summary, the results of the present study show that MALAT1 acts as a sponge for miR-181a and thereby regulates expression of HMGB2 and development of cardiac hypertrophy. The novel MALAT1/miR-181a/HMGB2 axis might play a crucial role in cardiac hypertrophy and serve as a new therapeutic target.

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Ethics Approval

All animal procedures were approved by the Animal Research Committee of Ganzhou People’s Hospital (approval No. SJTY(E) 2018-067)

Rights

Science and Technology Project of Jiangxi Province (No. 20203BBGL73188) -- Natural Science Foundation of Jiangxi, China (No. 20212ACB206031)

How to Cite

Chen, F. ., Li, W. ., Zhang, D. ., Fu, Y. ., Yuan, W. ., Luo, G. ., … Luo, J. (2022). MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway. European Journal of Histochemistry, 66(3). https://doi.org/10.4081/ejh.2022.3426
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