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Toxicol Lett. 2014 Mar 3;225(2):275-84. doi: 10.1016/j.toxlet.2013.12.008. Epub 2013 Dec 18.

Cell cycle changes mediated by the p53/miR-34c axis are involved in the malignant transformation of human bronchial epithelial cells by benzo[a]pyrene.

Author information

1
The First Clinic Medical College, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
2
Jiangsu Center for Disease Control and Prevention, Nanjing 210029, Jiangsu, PR China.
3
Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China.
4
Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu, PR China. Electronic address: drqzliu@hotmail.com.

Abstract

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 (12h) exposure to BaP, p-p53 was increased, and with increasing time of exposure (24h), the increase in p-p53 at a concentration of 1μM BaP was followed by a decline with increasing concentrations; wt-p53 and mt-p53 did not change. With prolonged exposure (48h), 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.

KEYWORDS:

Benzo[a]pyrene (BaP); Cell cycle; Malignant transformation; miR-34c; p53

PMID:
24362009
DOI:
10.1016/j.toxlet.2013.12.008
[Indexed for MEDLINE]

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