MicroRNAs (miRNAs) are small, non-protein-coding RNAs that can function as tumor 
suppressors or oncogenes. Deregulation of miRNA expression has been reported in 
lung cancer. However, modulation of miRNA expression by chemopreventive agents 
remains to be defined. In the present study, we examined if the chemopreventive 
agent indole-3-carbinol (I3C) reversed vinyl carbamate (VC)-induced deregulation 
of miRNA levels in lung tissues of female A/J mice. Lung tissues were obtained 
from a previous chemoprevention study, in which mice were treated with VC and 
given I3C in the diet for 15 weeks. Microarray studies revealed alterations in 
the expression of a number of miRNAs in lung tumors relative to that of normal 
lungs. miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently 
upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors 
relative to normal lungs. In mice treated with VC and given I3C in the diet, 
levels of miR-21, mir-31, miR-130a, miR-146b and miR-377 were reduced relative 
to the level in mice treated with the carcinogen only. The results of the 
microarray study were confirmed by quantitative reverse transcription-polymerase 
chain reaction and gel analysis of polymerase chain reaction products. Further 
studies with miR-21 indicated that phosphatase and tensin homolog, programmed 
cell death 4 and rich protein with Kazal motifs are potential targets for the 
oncogenic effect of miR-21 and the chemopreventive activity of I3C. Taken 
together, we showed here that miRNAs are deregulated during VC-induced mouse 
lung tumorigenesis and their levels are modulated by I3C. Therefore, miRNAs and 
their target genes are promising biomarkers for the diagnosis of lung cancer and 
efficacy of chemopreventive/chemotherapeutic agents.