MicroRNAs (miRNAs) are small, noncoding RNAs that play a crucial role in regulation of gene expression. Recent studies have shown that miRNAs implicated in initiation and progression of various human cancers, including breast cancer and also analysis of miRNA expression profiles in cancer provide new insights into potential mechanisms of carcinogenesis. Melatonin, N-acetyl-5-methoxytryptamine, is synthesized by the pineal gland in response to the dark/light cycle and has been known to act as a synchronizer of the biological clock. Melatonin has a variety of therapeutic effects, such as immunomodulatory actions, anti-inflammatory effects, and antioxidant actions. Furthermore, melatonin is reported to have an anticancer function including suppression of the metabolism of tumor cells and induction of tumor suppressor genes in cancer cells, including breast cancer cells. In this study, we determined whether miRNAs play a role in regulation of various gene expression responses to melatonin in MCF-7 human breast cancer cells. We examined whole-genome miRNA and mRNA expression and found that 22 miRNAs were differentially expressed in melatonin-treated MCF-7 cells. We further identified a number of mRNAs whose expression level shows a high inverse correlation with miRNA expression. The Gene Ontology (GO) enrichment analysis and pathways analysis were performed for identification of the signaling pathways and biological processes affected by differential expression of miRNA and miRNA-related genes. Our findings suggested that melatonin may modulate miRNA and gene expression as an anticancer mechanism in human breast cancer cells.

ABSTRACT. The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF + albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds. KEY WORDS: gene expression, microarray, peroxisome proliferators, phenytoin, toxicogenomics.J. Vet. Med. Sci. 66(11): 1329-1333, 2004 We are gaining information of numerous candidate genes that have been known and unknown their function in biological system through many projects has been done and are processing. Many techniques that are able to analyze many genes and proteins simultaneously in once are used to interpret the information. Microarray technology, one of them, permits the comparison of thousands of genes in different biological systems. Lately, microarray system has been used for the prediction of toxicity through gene expression induced toxicant [15,18] and has shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo [5] and in vitro system [2]. As these results, many pharmaceutical companies and research groups are making databases of gene expression related to toxic mechanism induced by compounds that were well characterized. These collected databases of microarray associated with toxicity will shorten the toxicity evaluation steps that are often the rate-limiting step in the discovery and development of new pharmaceuticals.In this study, we have used cDNA microarray methods for analysis of the effect of 3 compounds related to hepatotoxin including 2 peroxisome proliferators: clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2, 5-dimethyl-phenoxy] 2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5, 5-diphenylhydantoin). The peroxisome proliferators have been studied in many toxic study groups because most of peroxisome proliferators have hepatic toxicity. It has been shown that peroxisome proliferator activated receptors play a significant role in regulation of lipid metabolism, hepatic peroxisomal genes expression, insulin sensitivity and glucose homeostasis [8,9]. Also, it was known that phenytoin is an anticonvulsant and cardiac depressan...

finding pathway diagrams from the KEGG PATHWAY database. Array2KEGG has focused on simplicity in user interface, integration in heterogeneous biological databases, and visualization in depiction of a pathway diagram that includes more than two interesting genes. Array2KEGG is freely available for use at http://www. koreagene.co.kr/cgi-bin/service/service1.pl.

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