Journal
FEBS LETTERS
Volume 588, Issue 4, Pages 549-559Publisher
WILEY
DOI: 10.1016/j.febslet.2013.11.040
Keywords
Apoptosis; Bcl-2 associated X protein; B cell lymphoma-2; Capsaicin; DNA-damage; MiR-34a; Mitochondrial transmembrane potential; p53; Reactive oxygen species
Funding
- University Grant Commission (UGC)
- Department of Biotechnology (DBT)
- Council for Scientific and Industrial Research (CSIR)
- Department of Science and Technology (DST), Govt. of India
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Tumor-suppressive miR-34a, a direct target of p53, has been shown to target several molecules of cell survival pathways. Here, we show that capsaicin-induced oxidative DNA damage culminates in p53 activation to up-regulate expression of miR-34a in non-small cell lung carcinoma (NSCLC) cells. Functional analyses further indicate that restoration of miR-34a inhibits B cell lymphoma-2 (Bcl-2) protein expression to withdraw the survival advantage of these resistant NSCLC cells. In such a proapoptotic cellular milieu, where drug resistance proteins are also down-regulated, p53-trans-activated Bcl-2 associated X protein (Bax) induces apoptosis via the mitochondrial death cascade. Our results suggest that p53/miR-34a regulatory axis might be critical in sensitizing drug-resistant NSCLC cells. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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