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Restoration of p53/miR‐34a regulatory axis decreases survival advantage and ensures Bax‐dependent apoptosis of non‐small cell lung carcinoma cells
Author(s) -
Chakraborty Samik,
Mazumdar Minakshi,
Mukherjee Shravanti,
Bhattacharjee Pushpak,
Adhikary Arghya,
Manna Argha,
Chakraborty Sreeparna,
Khan Poulami,
Sen Aparna,
Das Tanya
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.11.040
Subject(s) - apoptosis , carcinoma , cancer research , small cell lung carcinoma , lung , cell survival , cell , microbiology and biotechnology , cell growth , chemistry , biology , medicine , small cell carcinoma , biochemistry , genetics
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.