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Examination of the Role of miR-23a in the Development of Thermotolerance

[ Vol. 20 , Issue. 3 ]

Author(s):

Rabih Roufayel and Seifedine Kadry*   Pages 194 - 201 ( 8 )

Abstract:


Background: Thermotolerance is an acquired state of increased heat resistance that occurs following exposure to non-lethal proteotoxic stress. A large body of evidences implicates that molecular chaperon members belonging to the heat shock protein family could be acting as potential mediators of the thermotolerant state.

Objective: Recent evidence has demonstrated heat shock proteins HSP90, HSP70 and HSP27 have inhibited heat-induced cell death by intervening at various steps in stressinduced apoptotic pathways. Previous studies have shown that HSP70 prevented heatinduced apoptosis by preventing the NOXA dependent decrease in MCL-1 levels leading to both BAX activation and cytochrome c release from mitochondria. We have also demonstrated that HSP70 expressing cells have enhanced levels of miR-23a prevent heat-induced increase in NOXA levels and suppress apoptosis.

Methods: Stably transfected cell lines expressing either a control shRNA or a miR-23a targeting shRNA are quantified using both RT-PCR and semi-quantitative RT-PCR to determine the effect of different hyperthermic exposure treatment on miR-23a and Noxa mRNA expression levels.

Results: This study shows that thermotolerant-induced pre-heat shock treatment is capable of increasing miR-23a levels. Furthermore, stable cell clones expressing a miR- 23a targeting shRNA having reduced miR-23a levels are incapable of developing a thermotolerance state, leading to apoptosis.

Conclusion: These results demonstrate the novel finding that miR-23a is an important factor in the development of the thermotolerant state.

Keywords:

Thermotolerance, apoptosis, heat shock protein, hyperthermia, HSP70, NOXA, miR-23ª.

Affiliation:

College of Engineering and Technology, American University of the Middle East, Department of mathematics and computer science, Faculty of Science, Beirut Arab University



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