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- W2200671444 endingPage "784" @default.
- W2200671444 startingPage "771" @default.
- W2200671444 abstract "Chemical carcinogenesis can be induced by genotoxic (GTX) or non-genotoxic (NGTX) carcinogens. GTX carcinogens have a well-described mode of action. However, the complex mechanisms by which NGTX carcinogens act are less clear and may result in conflicting results between species [e.g. Wy-14,643 (Wy)]. We hypothesise that common microRNA response pathways exist for each class of carcinogenic agents. Therefore, this study compares and integrates mRNA and microRNA expression profiles following short term acute exposure (24 and 48h) to three GTX [aflatoxin B1 (AFB1), benzo[a]pyrene (BaP) and cisplatin (CisPl)] or three NGTX (2,3,7,8-tetrachloordibenzodioxine (TCDD), cyclosporine A (CsA) and Wy) carcinogens in primary mouse hepatocytes. Discriminative gene sets, microRNAs (not for 24h) and processes were identified following 24 and 48h of exposure. From the three discriminative microRNAs found following 48h of exposure, mmu-miR-503-5p revealed to have an interaction with mRNA target gene cyclin D2 (Ccnd2 – 12444) which was involved in the discriminative process of p53 signalling and metabolism. Following exposure to NGTX carcinogens Mmu-miR-503-5p may have an oncogenic function by stimulating Ccnd2 possibly leading to a tumourigenic cell cycle progression. By contrast, after GTX carcinogen exposure it may have a tumour-suppressive function (repressing Ccnd2) leading to cell cycle arrest and to increased DNA repair activities. In addition, compound-specific microRNA–mRNA interactions [mmu-miR-301b-3p-Papss2 (for AFB1), as well as mmu-miR-29b-3p-Col4a2 and mmu-miR-24-3p-Flna (for BaP)] were found to contribute to a better understanding of microRNAs in cell cycle arrest and the impairment of the DNA damage repair, an important hallmark of GTX-induced carcinogenesis. Overall, our results indicate that microRNAs represent yet another relevant intracellular regulatory level in chemical carcinogenesis." @default.
- W2200671444 created "2016-06-24" @default.
- W2200671444 creator A5006442657 @default.
- W2200671444 creator A5018186238 @default.
- W2200671444 creator A5019324617 @default.
- W2200671444 creator A5019780216 @default.
- W2200671444 creator A5068366960 @default.
- W2200671444 creator A5073937073 @default.
- W2200671444 date "2015-05-14" @default.
- W2200671444 modified "2023-09-25" @default.
- W2200671444 title "Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes" @default.
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