Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells |
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Authors: | Samik Chakraborty Minakshi Mazumdar Shravanti Mukherjee Pushpak Bhattacharjee Arghya Adhikary Argha Manna Sreeparna Chakraborty Poulami Khan Aparna Sen Tanya Das |
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Affiliation: | 1. Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata 700054, West Bengal, India;2. Lady Brabourne College, P-1/2, Suhrawardy Ave, Kolkata, India |
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Abstract: | 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-transactivated 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. |
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Keywords: | Bax, Bcl-2 associated X protein Bcl-2, B cell lymphoma-2 CAM, complementary and alternative medicine CsA, cyclosporine A DAPI, 4&prime ,6-diamidino-2-phenylindole dihydrochloride DiOC6, 3,3 dihexyloxacarbonicaocyanine iodide micro RNA 34a, mitochondrial membrane potential, miR-34a MTP, mitochondrial transmembrane potential NAC, N-acetylcysteine NSCLC, non-small cell lung cancer p38MAPK, p38 mitogen activated protein kinase ROS, reactive oxygen species siRNA, short-interfering RNA shRNA, short-hairpin RNA |
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