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Molecular and Cellular Biochemistry

, Volume 417, Issue 1–2, pp 191–203 | Cite as

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

  • Satish K. Raut
  • Gurinder B. Singh
  • Bhawna Rastogi
  • Uma Nahar Saikia
  • Anupam Mittal
  • Nilambra Dogra
  • Sandeep Singh
  • Rishikesh Prasad
  • Madhu KhullarEmail author
Article

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.

Keywords

Apoptosis Cardiac hypertrophy Diabetic cardiomyopathy miR-30c miR-181a p53 

Notes

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.

Compliance with ethical standards

Conflict of Interest

The authors declare they have no conflict interests.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Satish K. Raut
    • 1
  • Gurinder B. Singh
    • 1
  • Bhawna Rastogi
    • 2
  • Uma Nahar Saikia
    • 3
  • Anupam Mittal
    • 4
  • Nilambra Dogra
    • 1
  • Sandeep Singh
    • 5
  • Rishikesh Prasad
    • 1
  • Madhu Khullar
    • 1
    Email author
  1. 1.Department of Experimental Medicine and BiotechnologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of OtolaryngologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Department of HistopathologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia
  4. 4.Department of CardiologyPost Graduate Institute of Medical Education and ResearchChandigarhIndia
  5. 5.Centre for Genetic Diseases and Molecular MedicineCentral University of PunjabBathindaIndia

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