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.