miR-30c and miR-181a synergistically modulate p53–p21 pathway in diabetes induced cardiac hypertrophy

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...

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Published in:Molecular and cellular biochemistry 2016-06, Vol.417 (1-2), p.191-203
Main Authors: Raut, Satish K., Singh, Gurinder B., Rastogi, Bhawna, Saikia, Uma Nahar, Mittal, Anupam, Dogra, Nilambra, Singh, Sandeep, Prasad, Rishikesh, Khullar, Madhu
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cardiology
Cardiomyocytes
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Diabetes
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetic Cardiomyopathies - metabolism
Diabetic Cardiomyopathies - pathology
Glucose
Heart
Heart hypertrophy
Life Sciences
Luciferase
Male
Medical Biochemistry
MicroRNA
MicroRNAs - metabolism
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Oncology
Rats
Rats, Wistar
Tumor proteins
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-016-2729-7