MicroRNAs are small non-coding RNAs that affect gene expression. They are essential in normal physiological processes and have been implicated in carcinogenesis. Hepatocellular carcinoma (HCC) is the second leading cause of cancer death globally, with the risk factor aflatoxin (AFB1) estimated to play a causal role in up to 28% of all HCC cases. In this study, we analyzed circulating miRNAs in a quantitative rat cancer model that were previously found to be associated with AFB1 exposure in liver. Sera were examined from 3 groups of animals: rats dosed with AFB1 (200 µg) for 28 consecutive days receiving vehicle only or AFB1 plus the chemopreventive agent CDDO-Im (30 µmol), and controls (Johnson et al., CaPR, 2014). Small RNAs were isolated from these serum samples at the end of the dosing period and analyzed by RT-qPCR. Quantitative PCR results at the end of the carcinogenic 28-day dosing regimen revealed notable increased expression of miR-34a-5p and miR-181c-3p (13 fold and 170 fold, respectively) in the AFB1 treated samples compared to controls. This expression was reduced in animals that received complete protection from developing HCC by concurrent intervention with CDDO-Im. Additionally, miR-122-5p displayed increased expression (5 fold) and miR-541-5p was downregulated (0.08 fold) in the sera of AFB1-treated animals. Overall, the data suggest that serum expression of miR-34a-5p and 181c-3p during liver cancer initiation could give insight into increased risk of developing HCC. Supported by T32ES007141-31A1 and CA197222.

Citation Format: Merricka C. Livingstone, Bill D. Roebuck, Natalie M. Johnson, Thomas W. Kensler, John D. Groopman. Elevated levels of circulating miR-34a-5p and miR-181c-3p during cancer initiation by aflatoxin B1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4448. doi:10.1158/1538-7445.AM2017-4448