Exp Mol Med.
2012 Dec;44(12):723-732.
Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-beta in colorectal cells
- Affiliations
-
- 1Department of Gastroenterology, Beijing Military General Hospital, Beijing 100700, People's Republic of China. Jianqiu@263.net
- 2Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
- 3Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Department of Epidemiology, School of Public Health, University of California, Los Angeles, California, USA. jrao@mednet.ucla.edu
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-beta mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-beta, 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-beta, which may be the basis for the anti-cancer effect in colorectal cells.
MeSH Terms
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Adaptor Proteins, Signal Transducing/genetics/metabolism
Adult
Aged
Cell Line, Tumor
Colorectal Neoplasms/*genetics/metabolism
DNA Mismatch Repair/*genetics
Estradiol/analogs & derivatives/blood/*pharmacology
Estrogen Antagonists/pharmacology
Estrogen Receptor beta/genetics/*metabolism
Female
*Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs/genetics/*metabolism
Middle Aged
MutS Homolog 2 Protein/genetics/metabolism
Nuclear Proteins/genetics/metabolism
RNA, Messenger/biosynthesis
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