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Altered microRNA expression induced by tumorigenic conazoles in mouse liver.
Citation:
ROSS, J. A., S. F. Thai, M. J. KOHAN, C. JONES, C. F. BLACKMAN, Z. Li, AND T. Chen. Altered microRNA expression induced by tumorigenic conazoles in mouse liver. Presented at American Association for Cancer Research, Washington, DC, April 17 - 21, 2010.
Impact/Purpose:
This study represents the characterization of a microRNA signature that differentiates tumorigenic from nontumorigenic conazoles.
Description:
Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumorigenicity, we analyzed the microRNA expression levels in control and conazole treated mice after 90 days of administration in feed. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the Significance Analysis of Microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q s 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the non-tumorigenic conazole. A group of 19 miRNAs was identified whose expression was significantly altered in both triadimefon and propiconazole treated animals but not in myclobutanil treated animals. All but one of the altered miRNAs were downregulated compared to controls. The greatest fold-changes in miRNA expression were observed for mmu-mir-135b and mmu-mir-684. Among the putative targets of the miRNAs altered by tumorigenic conazoles are genes involved in regulation of apoptosis and cell proliferation. This abstract does not reflect US EPA policy.