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Differential MicroRNA Profiles of Spontaneous and Induced Hepatocellular Carcinomas in Male B6C3F1 Mice.
Citation:
Carswell, G., S. Hester, W. Ward, H. Ren, A. Deangelo, C. Wood, AND B. Chorley. Differential MicroRNA Profiles of Spontaneous and Induced Hepatocellular Carcinomas in Male B6C3F1 Mice. Presented at Epigenetics Marks and Cancer Drugs, March 20 - 25, 2013.
Impact/Purpose:
This abstract will be presented at the Epignetics Marks and Cancer Drugs, March 20-25, 2012, Sante Fe, NM
Description:
Epigenetic processes have key roles in regulating transcriptional patterns and cellular functions related to chemical carcinogenesis. MicroRNAs (miRNAs) are attractive epigenetic biomarkers given their mechanistic roles in tumorigenesis, tissue-specificity, and small size, which convey resistance to degradation and fragmentation. Here, we examined global miRNA expression in non-neoplastic liver and hepatocellular carcinomas from 2 year-old rnale B6C3F1 mice. Carcinomas occurred spontaneously (in the control group) or following treatment in the drinking water with two reference mouse liver tumorigens, dichloroacetic acid (DCA; by-product of drinking water chlorination) and phenobarbital (PB; barbiturate and CAR/PXR activator). PB (0.06%) was given continuously for 100 wks while DCA (3.5 g/L) was given as a stop-treatment for 1Owks followed by 90 weeks of water. miRNA was measured using Affymetrix miRNA 3.0 arrays. Principal component analysis (PCA) of normalized global mouse miRNA values (by Robust Microarray Analysis + Detection Above Background) grouped PB-induced, DCA induced, and spontaneous (control) tumors from non-tumorigenic samples. Expression contrasts (examined by Bayesian t-test and Benjamini-Hochberg multi-test correction, q<0.05) identified a 7-miRNA panel that distinguished PB-induced tumor from non-neoplastic PB liver, DCA-induced and spontaneous liver tumors. PCA using this miRNA panel further defined 3 groupings: (1)OCA/spontaneous tumors, (2) PB-induced tumors and (3) non-neoplastic liver. Some of these miRNA, including miR-31, miR-127, miR-379 and miiR-690, have known links to cancer establishment and progression, while others such as miR-3077* have putative gene targets in the CAR pathway such as Cyp2b10. Future studies will seek to validate and test this panel of candidate miRNA markers. Our findings support the idea that miRNA biomarkers may be used to characterize specific molecular phenotypes related to environmental chemical induced tumorigenesis. This abstract does not necessarily reflect the policies of the US EPA.