4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Circulating MicroRNA Deregulation in Early Lung Carcinogenesis

ObjectiveTo study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced early stage lung carcinogenesis.MethodsA lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.ResultsNo lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.ConclusionThe expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.