miR‐200a‐5p augments cardiomyocyte hypertrophy induced by glucose metabolism disorder via the regulation of selenoproteins

Abstract

Selenium and selenoproteins are identified as potential determinants in pathological cellular hypertrophy. Cardiomyocytes hypertrophy is a compensatory form of heart disease characterized by increased size of cardiomyocytes. However, the link between cardiac hypertrophy and Se-specific microRNA (miRNA) remains to be characterized. In the current study, we established a miR-200a-5p mimic and an inhibitor cardiomyocytes model. Cardiomyocytes hypertrophy was induced in the miR-200a-5p mimic group. Hence, we detected the glucose level of cardiomyocytes to estimate the cellular glucose uptake. The effect of miR-200a-5p overexpression and the low expression on 25 selenoproteins mRNA levels was further explored using reverse transcription polymerase chain reaction. Overexpression of miR-200a-5p elevated glucose uptake and Txnrd2, 3 expression and reduced Sepp1, Seln, Selt, and Sep15 expression in cardiomyocytes. Contrary results were observed in cardiomyocytes with the knockdown of miR-200a-5p. We next assessed glucose metabolism-related genes in cardiomyocytes. The results showed that miR-200a-5p had a negative correlation with insulin-like growth factor gene-1, insulin-like growth factor binding protein (IGFBP)1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 and had a positive correlation with Akt, glucose transporter family (GLUT)2, GLUT3, and GLUT4. These results support the involvement of selenoproteins and glucose metabolism in the control of cardiomyocytes hypertrophy by Se-specific miRNA, suggesting that miR-200a-5p inhibited the expression of stress-related selenoproteins to alter glucose transport leading to glucose metabolism disorder, eventually inducing cardiomyocytes hypertrophy. Our finding highlights a pivotal role of Se-specific miRNA and selenoproteins in cardiac hypertrophy.

The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk

“…Further, circulating miR-200c correlates with cardiac hypertrophy and diastolic dysfunction as assessed by E/e ′ and miR-200a with cardiac hypertrophy and arterial stiffness. In light of the findings of the present work and of the previously described negative effects of miR-200c and miR-200a on endothelial [24,25,29,63] and vascular smooth muscle cells [31] and cardiac [45][46][47] function, the upregulation of these miRNAs could play a role in the inflammation and oxidative stress upregulation, increasing the risk of adverse CV events in psoriatic patients.…”

“…Moreover, miR-200c and miR-200a have been recently associated with cardiac hypertrophy in animal models [45][46][47]; further, both miR-200c and miR-200a target SIRT1 [25,53], and in addition, we demonstrated that miR-200c targets eNOS, contributing to endothelial dysfunction establishment increasing ROS and decreasing NO, that is a potent vasodilator necessary for endothelial function preservation…”

“…Since miR-200a was also found to be upregulated in cardiomyocyte hypertrophy [47], we wondered whether its circulating levels correlated with CV risk.…”

Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients

“…59 In particular, the expression of miR-200a-5p is significantly increased in several cancer types 44,45,47 and heart diseases. 63,64 In our study, miR-200a-5p has been shown to regulate TAP1 expression in HEK293T and melanoma cells. MiR-200a-5p was initially found by in silico prediction to bind Figure 8.…”

An Overview of the Role of Calcium/Calmodulin-Dependent Protein Kinase in Cardiorenal Syndrome

“…In addition, it is extremely important to highlight the role of micro RNA (miR). miR is a short and noncoding RNA that interacts with the 3-untranslated region (UTR) of mRNAs blocking gene expression, degrading mRNAs and regulating protein expression ( Winter et al, 2009 ; Krol et al, 2010 ; Qi et al, 2019 ; Yang et al, 2019 ).…”