Abstract
Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-β mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-β, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-β, which may be the basis for the anti-cancer effect in colorectal cells.
Highlights
Colorectal cancer (CRC) is the fourth most common cause of death from cancer, affects around 1.2 million people world wide, with about 608,700 fatalities per year (Ferlay et al, 2010)
To determine if the reduction of these miRNAs by E2 was mediated by estrogen receptor, COLO205 cells were pre-incubated with 100 nM estrogen antagonist ICI182,780 for 6 h, followed by E2 incubation
The findings suggest that the differential effect of E2 on miRNA expression in different cell lines relates to the estrogen receptor (ER)-β, or the ratio of ER-β to ER-α
Summary
Colorectal cancer (CRC) is the fourth most common cause of death from cancer, affects around 1.2 million people world wide, with about 608,700 fatalities per year (Ferlay et al, 2010). Both the prevalence (Ries et al, 2000) and the lifetime risk of CRC (Froggatt et al, 1999) are significantly lower in females than in males. This is true when comparing pre-menopausal women to age-matched men. Decreased ER-β expression may lead to hyperproliferation, decreased differentiation, and decreased apoptosis of colonic epithelial cells (Maria and Paola, 2008), suggesting that ER-β is likely to be involved in the regulation of colonic tumor growth
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