Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong; Department of Cardiology, Ganzhou People's Hospital, Nanchang University, Ganzhou, Jiangxi .
Department of Cardiology, Ganzhou People's Hospital, Nanchang University, Ganzhou, Jiangxi.
Eur J Histochem. 2022 Jun 21;66(3):3426. doi: 10.4081/ejh.2022.3426.
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.
非编码 RNA 对于心脏肥大的调控非常重要。MALAT1（一种长链非编码 mRNA）、miR-181a 和 HMGB2 的功能；它们在心脏肥大中的贡献；以及它们在这个过程中的调节关系尚不清楚。在本研究中，我们用血管紧张素 II（Ang II）处理原代心肌细胞，模拟心脏肥大。与对照心肌细胞相比，Ang II 处理的心肌细胞中 MALAT1 的表达明显下调。MALAT1 的过表达抑制 Ang II 诱导的心肌肥大，而 MALAT1 的基因敲低则促进心肌肥大。双荧光素酶报告基因实验表明，MALAT1 作为 miR-181a 的海绵体，在心脏肥大过程中抑制其表达。miR-181a 抑制剂的过表达抑制了心脏肥大，而过表达 miR-181a 模拟物则增强了心脏肥大。HMGB2 在心脏肥大过程中下调，并通过生物信息学分析和双荧光素酶报告基因实验鉴定为 miR-181a 的靶标。miR-181a 的过表达降低了 HMGB2 的 mRNA 和蛋白水平。挽救实验表明，MALAT1 的过表达逆转了 miR-181a 对 HMGB2 表达的影响。综上所述，本研究结果表明，MALAT1 作为 miR-181a 的海绵体，从而调节 HMGB2 的表达和心脏肥大的发生。新发现的 MALAT1/miR-181a/HMGB2 轴可能在心脏肥大中发挥关键作用，并可能成为新的治疗靶点。
