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

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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.

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Acknowledgments

This research was supported by the Department of Science and Technology (SR/SO/HS-0049/2010). Satish K Raut is a PhD student in Department of Experimental Medicine and Biotechnology, PGIMER and was supported by Indian Council of Medical Education and Research (3/1/2(13)/CVD/2010/NCD-II), New Delhi, India.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Satish K. Raut, Gurinder B. Singh, Nilambra Dogra, Rishikesh Prasad & Madhu Khullar

  2. Department of Otolaryngology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Bhawna Rastogi

  3. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Uma Nahar Saikia

  4. Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Anupam Mittal

  5. Centre for Genetic Diseases and Molecular Medicine, Central University of Punjab, Bathinda, 151001, India

    Sandeep Singh

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  1. Satish K. Raut
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Correspondence to Madhu Khullar.

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Raut, S.K., Singh, G.B., Rastogi, B. et al. miR-30c and miR-181a synergistically modulate p53–p21 pathway in diabetes induced cardiac hypertrophy. Mol Cell Biochem 417, 191–203 (2016). https://doi.org/10.1007/s11010-016-2729-7

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