Epigenetic Regulation of miR-22 in a BPA-exposed Human Hepatoma Cell

Abstract

Bisphenol A (BPA), an widely used environmental chemical, is encircled to human life. However, we generally do not know whether or not it can cause negative health effects. One of the representative epigenetic changes that inhibit gene expression is DNA methylation, which has been very well studied in association with cancer and development. Gene function is changed by DNA methylation; however, its genetic code does not change. Our study hypothesized that a post-transcriptional change in DNA occurs due to exposure to BPA. These changes then cause regulation of microRNA and gene expression. To identify these successional regulations, we conducted microarraybased assays. For validation, also we conducted bisulfite sequencing, quantitative real-time PCR, miRNA inhibitor assay, and Western blotting. We found 1,751 hypo-methylation changed regions, and several micro- RNA had included methylated-regions. miR-22 was also hypomethylated (chr17:1563947-1564031) by BPA-exposure, and expression of miR-22 was up-regulated in an miRNA array and real-time PCR. miR- 22 has been reported to inhibit estrogen signaling by direct targeting of the estrogen receptor alpha mRNA. Taking notice of this point, we analyzed gene expression profiles that included its predicted targets. In the present study, we found the cause of hypomethylation of miR-22 and negative regulation of its apoptosisrelated target gene expression by BPA-exposure. These results suggests that BPA can alter sequential genomic appearances in HepG2 cells, a potentially affection of BPA toxicity. Also, the results of our study support that toxicology study need to integrated analysis of array-based assays for help in understanding of the molecular action of environmental toxicants.