Altered miRNA Expression Profiles and miR-1a Associated With Urethane-Induced Pulmonary Carcinogenesis

Abstract

MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene expression. Previous research has suggested that aberrant miRNA expression often plays a critical role in many types of cancer, including lung cancer. However, the exact miRNAs that are involved in pulmonary carcinogenesis remain unclear. We investigated the miRNA-based molecular changes that occur in urethane-induced carcinogenicity and identified specific miRNA deregulation in pulmonary carcinogenesis induced by urethane. In this study, we used a lung cancer model in which Balb/c mice were exposed to urethane via ip injection once a week for four consecutive weeks. The mice were then killed in weeks 6, 12, or 24. Two small RNA libraries were constructed with the total RNA from the lung tumor and normal adjacent lung tissues of the urethane-injected mice collected in week 24. Using Solexa sequencing, we identified a plethora of differentially expressed miRNAs and predicted nine novel miRNAs. Further analysis demonstrated the sustainable downregulation of miR-1a in the lung tissues in lung carcinogenesis induced by urethane. The levels of miR-1a were also reduced in the serum. Our findings indicate that urethane exposure alters the expression of a cluster of miRNAs. The simultaneous downregulation of miR-1a in lung tissues and serum in urethane-induced pulmonary carcinogenesis suggests that miR-1a is associated with tumorigenesis.