miR-30c and miR-181a synergistically modulate p53?p21 pathway in diabetes induced cardiac hypertrophy
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Date
2016
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Springer New York LLC
Abstract
p53?p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53?p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53?p21 pathway in DbCM. ? 2016, Springer Science+Business Media New York.
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Keywords
Microrna, Microrna 181A, Microrna 30C, Protein P21, Protein P53, Unclassified Drug, Cdkn1A Protein, Rat, Cyclin Dependent Kinase Inhibitor 1A, Microrna, Mirn181 Microrna, Rat, Mirn30 Microrna, Rat, Protein P53, Animal Cell, Animal Experiment, Animal Model, Animal Tissue, Apoptosis Cardiac Muscle Cell, Cell Size, Controlled Study, Diabetes Mellitus, Diabetic Cardiomyopathy, Diabetic Patient, Disease Association, Enzyme Inhibition, Gene Expression, Heart Ventricle Hypertrophy, Human, Hum
Citation
Raut, S. K., Singh, G. B., Rastogi, B., Saikia, U. N., Mittal, A., Dogra, N., . . . Khullar, M. (2016). miR-30c and miR-181a synergistically modulate p53?p21 pathway in diabetes induced cardiac hypertrophy. Molecular and Cellular Biochemistry, 417(1-2), 191-203. doi: 10.1007/s11010-016-2729-7