Differential epigenetic signatures between normal uterine smooth muscle cells (SMC) and leiomyoma cells (LM) and their association with estrogen responses
Description
Differential gene expression between uterine leiomyoma (fibroids) and adjacent normal smooth muscle has been found in clinical tissues and cell cultures. The purpose of this study is to investigate whether there are differential epigenetic signatures and their involvement in differential gene expression, apoptosis and estrogen responses between two uterine stable cell lines, uterine leiomyoma UtLM-hT (LM) and normal uterine smooth muscle cell lines UtSM-hT (SMC). We first analyzed DNA methylation status using a cancer methylation panel bead array and our data showed that there are differential methylation patterns between the two cell lines. We then selected nine genes with significant differential methylation patterns from the bead array and verified that eight of the nine selected genes show significant differential gene expression between the two cell lines. Additionally, four of the eight genes that demonstrate differential gene expression respond to treatment with a demethylation agent, 5-Aza-2'-deoxycytidine (DAC). Cellular retinol binding protein 1 (CRBP-1) and Tumor necrosis factor super family 10 (TNFSF10) are genes that shows significant differential methylation patterns, gene expression, and responses to DAC between LM and SMC. Altered extracellular matrix (ECM) genes and reduced apoptosis are found in LM and are associated with epigenetic silenced CRBP-1 and TNFSF10 genes. Hypersensitivity to estrogen was not changed with epigenetic modification in leiomyoma. However, differential Fos gene expression, before and after E2 treatment, between LM and SMC were both reduced after epigenetic modifications This is the first study to investigate systemically with a methylation bead array the possible role of epigenetic changes and their associated biological impacts and potential epigenetic therapy in uterine leiomyoma