MicroRNAs miR-221 and miR-181c regulation of liver tumor growth and metastasis in mouse progeny from Dibenzo[def,p]chrysene dosed mothers fed a sulforaphane diet
Dibenzo[def,p]chrysene (DBC) is a polycyclic aromatic hydrocarbon (PAH) and an IARC classified 2A probable human carcinogen. Mouse progeny transplacentally exposed to DBC have been shown to develop lung and liver tumors, with liver tumors developing predominantly in males later in life. Sulforaphane (SFN) is an isothiocyanate that plays a crucial role in cellular protection from carcinogens and can be found in cruciferous vegetables. MicroRNAs (miRNAs) are a class of small, <200bp, non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence has shown that miRNAs play critical roles in the development and progression of hepatocellular carcinoma (HCC). Pregnant mice were given one dose of DBC (15mg/kg) on gestation day (GD) 17 while fed a control or SFN diet (400ppm) starting on GD 9 and continued through weaning. Weaned offspring were maintained for 10 months and tissues analyzed for tumors. In this experiment, it was found that miR-181c was significantly up-regulated in both treatment groups. miR-221 was found to be significantly upregulated in the DBC/SFN treatment group. Proteins that are targeted by miR-181c have been shown to inactivate mechanisms which oncogenes use to metastasize in tissues. [Chen, Wang, Xu, Guo, Jiang, 2015] The upregulation of miR-181c and miR-221 suggests these miRNAs may be involved in hepatic cancer development in this model. Future research will explore candidate targets for mRNA level and protein expression thought to be regulated by these miRNAs
