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Genome‐wide profiling in melatonin‐exposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin
Author(s) -
Lee Seung Eun,
Kim Seung Jun,
Yoon HyoJeong,
Yu So Yeon,
Yang Hana,
Jeong Seong Il,
Hwang Seung Yong,
Park CheungSeog,
Park Yong Seek
Publication year - 2013
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2012.01027.x
Subject(s) - dna methylation , melatonin , epigenetics , biology , carcinogenesis , cancer research , methylation , breast cancer , bisulfite sequencing , microbiology and biotechnology , gene expression profiling , gene expression , gene , cancer , genetics , endocrinology
Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin‐induced differential expression of mi RNA and mi RNA ‐related genes in human breast cancer cell lines that indicated an anticancer effect of melatonin. In this report, we further characterized epigenetic changes in melatonin‐exposed MCF ‐7 cells through the analysis of DNA methylation profiles in breast cancer cells to provide new insights into the potential mechanisms of the anticancer effect of melatonin. Microarray‐based DNA methylation and gene expression profiling were carried out using human breast cancer cell lines. We further identified a number of mRNA s whose expression levels show an inverse correlation with DNA methylation levels. The mRNA expression levels and methylation status of candidate genes in melatonin‐exposed cells were confirmed by real‐time quantitative PCR and bisulfite PCR . This approach led to the detection of cancer‐related genes, which were oncogenic genes, including EGR 3 and POU 4F2/Brn‐3b were down‐regulated, while the tumor suppressor gene, GPC 3, was up‐regulated by 1 n m melatonin‐treated MCF ‐7 cells. Our results provide detailed insights into the DNA methylation patterns induced by melatonin and suggest a potential mechanism of the anticancer effect of aberrant DNA methylation in melatonin‐treated breast cancer cells.