• Studying the expression levels of two P53-associated lncRNAs under hyperglycemic conditions in bone marrow mesenchymal stem cells
  • Sanaz Tavakoli,1,* Mahshid Hojat,2 Hamidreza Vaziri,3
    1. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
    2. Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences(TUMS),Tehran, Iran
    3. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran


  • Introduction: Diabetes mellitus is the most common metabolic disease in humans that is characterized by chronic hyperglycemia and alteration of cellular homeostasis. Increased oxidative stress is a key factor in the pathogenesis of this disease. Recent studies demonstrated that elevation of glucose metabolism causes DNA double-strand breaks and activation of p53. Long non-coding RNAs (lncRNAs) are involved in the regulation of the DNA damage/repair network. LincRNA-RoR (RoR) is a strong negative regulator of p53 while DINO is required for p53-dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage. Still, the role of lncRNAs in hyperglycemic condition is not known. In this study, the expression level of ROR and DINO were evaluated in mesanchymal stem cells after exposure to hyperglycemia.
  • Methods: Cells were treated with 30 and 40 mM glucose for 3 days followed by DNA damage evaluation through comet assay. The gene expression of p53 and lncRNAs were evaluated using Real-Time PCR.
  • Results: The results of commet assay showed increased in DNA olive tail moment as an indicator of DNA damage after exposure to different concentration of glucose. P53 was increased in expression in hyperglycemic condition. Also, there was a notable increase in the expression of DINO and reduction in ROR expression in response to 30 and 40 mM glucose compared to control group (p<0.0001).
  • Conclusion: This finding showed a detrimental effect of hyperglycemia on DNA integrity of bone marrow derived mesenchymal stem cell and suggest a role for DINO and ROR as masters regulator of P53 signalling in hyperglycemia induced-DNA damage. Further studies are still needed to dissect the precise role of these lncRNAs.
  • Keywords: Diabetes, MSC, DNA damage, ROS, LncRNAs, ROR, DINO