Previous study suggests that microRNA (miRNA) expression is controlled in part by epigenetic machinery.5-Aza-CdR is an effective DNA demethylating agent widely used to reactivate tumor suppressor gene silenced by DNA hypermethylation.Resveratrol is one of the most popular dietary supplements consumed in the USA.Although resveratrol has drawn considerable attention for its potential in cancer prevention, the mechanism of its anticancer action is poorly understood.miRNA can act either as tumor suppressor or oncogene by regulating the behavior of cancer cells.Since tumor suppressor genes can be inactivated by DNA hypermethyation, we hypothesized that 5-Aza-CdR and resveratrol would inhibit cancer cell growth through the regulation of miRNA expression in which the deregulated miRNA expression is associated with epigenetic modification.The specific aims of this study are to: (1) investigate whether the expression of miRNAs are changed after 5-Aza-CdR and resveratrol intervention in breast cancer cell lines, and (2) examine DNA methytation status for genes that encode the altered expressed miRNAs.METHODS: Breast cancer cell lines Hs578T, T47D, MCF-7 and MDA-MB-231 were treated with resveratrol at 10uM for 25 days and 5-Aza-CdR at 5uM for six days respectively.RNA prepared from the cell lines was subjected to global miRNA profiling with microarray approaches followed by qRT-PCR validation.DNA methylation status of miRNA rniR-196a-1, miR-210 and miR-429 genes that encode deregulated rniRNAs was checked with Methylation Specific Real-time PCR techniques.RESULTS: AND CONCLUSION: Global miRNA profiling revealed 57 deregulated miRNAs induced by 5-Aza-CdR in Hs578T cells, and 32 deregulated miRNAs induced by resveratrol from the four breast cancer cell lines.35 altered miRNAs were subjected to qRT-PCR validation, and among them eight miRNAs treated with 5-Aza-CdR and three miRNAs treated with resveratrol were recorded with ≥2 in fold change.The methylation levels of miRNA miR-196a-1,-210 and-429 genes were significantly reduced and the expressions of miR-196a-1,-210 and -429 were increased after 5-Aza-CdR intervention.But the similar changes were not detected after resveratrol interference.miRNAs identified in this study may offer new markers for evaluation of chemoprevention efficiency or serve as therapeutic targets for breast cancer.