title: miR-30c and miR-181a synergistically modulate p53-p21 pathway in diabetes induced cardiac hypertrophy.
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.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Raut
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Gurinder B
authors.initials: GB
authors.lastname: Singh
authors.affiliation: Department of Otolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Bhawna
authors.initials: B
authors.lastname: Rastogi
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Uma Nahar
authors.initials: UN
authors.lastname: Saikia
authors.affiliation: Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Mittal
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Nilambra
authors.initials: N
authors.lastname: Dogra
authors.affiliation: Centre for Genetic Diseases and Molecular Medicine, Central University of Punjab, Bathinda, 151001, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Rishikesh
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. madhu.khullar@gmail.com.
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; C581717:MIRN181 microRNA, rat; C556157:MIRN30 microRNA, rat; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; Cardiac hypertrophy; Diabetic cardiomyopathy; miR-181a; miR-30c; p53