MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes

Vishalakshi Chavali, Suresh C. Tyagi, Paras K. Mishra

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We tested the hypothesis that miR-133a regulates DNA methylation by inhibiting Dnmt-1 (maintenance) and Dnmt-3a and -3b (de novo) methyl transferases in diabetic hearts by using Ins2+/- Akita (diabetic) and C57BL/6J (WT), mice and HL1 cardiomyocytes. The specific role of miR-133a in DNA methylation in diabetes was assessed by two treatment groups (1) scrambled, miR-133a mimic, anti-miR-133a, and (2) 5mM glucose (CT), 25mM glucose (HG) and HG+miR-133a mimic. The levels of miR-133a, Dnmt-1, -3a and -3b were measured by multiplex RT-PCR, qPCR and Western blotting. The results revealed that miR-133a is inhibited but Dnmt-1 and -3b are induced in Akita suggesting that attenuation of miR-133a induces both maintenance (Dnmt-1) - and de novo - methylation (Dnmt-3b) in diabetes. The up regulation of Dnmt-3a in Akita hearts elicits intricate and antagonizing interaction between Dnmt-3a and -3b. In cardiomyocytes, over expression of miR-133a inhibits but silencing of miR-133a induces Dnmt-1, -3a and -3b elucidating the involvement of miR-133a in regulation of DNA methylation. The HG treatment up regulates only Dnmt-1 and not Dnmt-3a and -3b suggesting that acute hyperglycemia triggers only maintenance methylation. The over expression of miR-133a mitigates glucose mediated induction of Dnmt-1 illustrating the role of miR-133a in regulation of DNA methylation in diabetes.

Original languageEnglish (US)
Pages (from-to)668-672
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number3
DOIs
StatePublished - Aug 31 2012

Fingerprint

DNA Methylation
MicroRNAs
Cardiac Myocytes
Medical problems
Methylation
Maintenance
Glucose
Up-Regulation
Multiplex Polymerase Chain Reaction
Transferases
Hyperglycemia
Western Blotting

Keywords

  • Dnmt-1
  • Dnmt-3
  • Epi-miRNA
  • Epigenetic modification
  • HL1 cardiomyocytes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. / Chavali, Vishalakshi; Tyagi, Suresh C.; Mishra, Paras K.

In: Biochemical and Biophysical Research Communications, Vol. 425, No. 3, 31.08.2012, p. 668-672.

Research output: Contribution to journalArticle

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