Abstract
MicroRNAs (miRNAs) represent a class of naturally occurring small noncoding RNA molecules that regulate genes by either inducing mRNA degradation or inhibiting translation. The expression of miRNAs is deregulated in several cancers, including lung cancer. However, most studies have been carried out using full‐blown cancer tissues and the regulation of miRNAs during early‐stage tumorigenesis is unknown. In the present study, we used an in vitro model of lung tumorigenesis to assess the effect of chronic treatment with tobacco compounds on the expression of miR‐21, one of the most deregulated miRNAs in lung cancer, in human bronchial epithelial cells (HBEC). Freshly prepared NNK (10 µM) and nicotine (10 µM) were added to the culture media containing NHBC every 3 days for 3 weeks. Beginning the second week of NNK plus nicotine treatment, the dietary chemopreventive agent diindolylmethane (DIM) was added, every 3 days, to the culture media until the termination of the study. Then, the cells were harvested, RNA prepared and the expression level of miR‐21 and its target genes PDCD4 and RECK were analyzed by QRT‐PCR. Levels of PDCD4 and RECK were also examined by Western immunoblotting. NNK plus nicotine treatment significantly elevated miR‐21 levels but markedly decreased expression of PDCD4 and RECK at both gene and protein levels. The effect of the tobacco compounds on miR‐21 as well PDCD4 and RECK was reversed by treatment with DIM. This study shows that miR‐21 levels are deregulated beginning the early phase of lung tumorigenesis and miR‐21 is a valuable target for chemopreventive agents.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-06.
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