Journal
TOXICOLOGY LETTERS
Volume 225, Issue 2, Pages 275-284Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2013.12.008
Keywords
Benzo[a]pyrene (BaP); p53; miR-34c; Malignant transformation; Cell cycle
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Funding
- Natural Science Foundations of China [30872146, 81072327, 81273114]
- Research Fund for the Doctoral Program of Higher Education of China [20103234110005]
- Key Program of Educational Commission of Jiangsu Province of China [11KJA330002]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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Characterization of aberrant microRNA (miRNA) expression during carcinogen-induced cell transformation will lead to a better understanding of the role of miRNAs in cancer development. In this investigation, we evaluated changes in p53 function and its downstream target miRNAs in benzo[ a] pyrene (BaP)induced transformation of human bronchial epithelial (HBE) cells. Chronic exposure to BaP induced malignant transformation of cells, in which there were increased levels of mutant p53 (mt-p53) and reduced expression of wild-type p53 (wt-p53) and phosphorylated p53 (p-p53). With acute (12 h) exposure to BaP, p-p53 was increased, and with increasing time of exposure (24 h), the increase in p-p53 at a concentration of 1 mu M BaP was followed by a decline with increasing concentrations; wt-p53 and mt-p53 did not change. With prolonged exposure (48 h), p-p53 and wt-p53 decreased, but mt-p53 increased. At different exposure times, the levels of miR-34c were consistent with p-p53. Over-expression of miR-34c resulted in inhibition of the BaP-induced G1-to-S transition and diminished up-regulation of cyclin D. Further, up-regulation of miR-34c or silencing of cylin D prevented BaP-induced malignant transformation. Thus, changes in the cell cycle mediated by the p53/miR-34c axis are involved in the transformation cells induced by BaP. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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