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

Author(s): Rabih Roufayel, Seifedine Kadry*

Journal Name: Current Molecular Medicine

Volume 20 , Issue 3 , 2020

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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.

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Article Details

Year: 2020
Page: [194 - 201]
Pages: 8
DOI: 10.2174/1566524019666191021111028
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