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

Abstract

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.

<strong></strong>An In-Depth Insight into Clinical, Cellular and Molecular Factors in COVID19-Associated Cardiovascular Ailments for Identifying Novel Disease Biomarkers, Drug Targets and Clinical Management Strategies

“…Xu et al have recently identified many genes that are differently expressed in cardiomyocytes and vascular endothelial cells of heart patients infected with COVID-19, including MALAT1, CD36, LARGE1, RYR2, PLCG2 (in cardiomyocytes), MALAT1, ID1, ID3, MT-CO1 and EGFL7 (in vascular endothelial cells) (87) . These genes regulate many vital functions in these cardiac cells (88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103) . The discovery of these novel contributors of COVID-19 mediated cardiac pathophysiology may help identify novel therapeutic targets.…”

Using Machine Learning Methods in Identifying Genes Associated with COVID-19 in Cardiomyocytes and Cardiac Vascular Endothelial Cells

“…Increased MALAT1 expression enhances cardiomyocyte apoptosis [50,82,83], and MALAT1 is highly expressed in patients with acute myocardial infarction [84,85]. However, the low expression of MALAT1 may promote myocardial hypertrophy [86].…”

“…Low MALAT1 expression in cardiomyocytes can cause damage to the hearts of COVID-19 patients. Chen et al [86] found that MALAT1 knockout exacerbates angiotensin II-induced cardiac hypertrophy, suggesting that patients with COVID-19 are susceptible to myocardial hypertrophy. As for the second parameter, TTN (ENSG00000155657), which was shown downregulated in this rule, was used in distinguishing patients with COVID-19.…”

The regulatory activities of MALAT1 in the development of bone and cartilage diseases

“…Similarly, MALAT1 acts as a sponge to inhibit miR-181a, which is up regulated in angiotensin II-treated cardiomyocytes. Decreased expression of MALAT1 promotes miR-181a-induced cardiac hypertrophy by decreasing the expression of HMGB2 (33). By sequestering miRNAs, MALAT1 The roles of MALAT1 in bone and cartilage diseases.…”

“…Similarly, MALAT1 acts as a sponge to inhibit miR-181a, which is up regulated in angiotensin II-treated cardiomyocytes. Decreased expression of MALAT1 promotes miR-181a-induced cardiac hypertrophy by decreasing the expression of HMGB2 ( 33 ). By sequestering miRNAs, MALAT1 may directly/indirectly regulate the pathophysiological processes of many diseases, providing a potential target for clinically therapeutic management ( Figure 1 ).…”