title: Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-β in colorectal cells.
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.
authors.affiliation: Department of Gastroenterology, Beijing Military General Hospital, Beijing 100700, People's Republic of China.
authors.forename: Yu-qi
authors.initials: YQ
authors.lastname: He
authors.forename: Jian-qiu
authors.initials: JQ
authors.lastname: Sheng
authors.forename: Xian-long
authors.initials: XL
authors.lastname: Ling
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yen
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D053843:DNA Mismatch Repair / Q000235:genetics*; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; C544965:MIRN135 microRNA, human; C501486:MLH1 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein