Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-beta in colorectal cells.
- Author:
Yu Qi HE
1
;
Jian Qiu SHENG
;
Xian Long LING
;
Lei FU
;
Peng JIN
;
Lawrence YEN
;
Jianyu RAO
Author Information
1. Department of Gastroenterology, Beijing Military General Hospital, Beijing 100700, People's Republic of China. Jianqiu@263.net
- Publication Type:Research Support, Non-U.S. Gov't ; Original Article
- Keywords:
colon neoplasms;
DNA mismatch repair;
estrogen receptor beta;
estrogen;
microRNAs
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(12):723-732
- CountryRepublic of Korea
- Language:English
-
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.
