Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-β in colorectal cells

다국어 초록 (Multilingual 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. E2inhibited 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.

참고문헌 (Reference)

1 Lanza G, "mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer" 6 : 54-, 2007

2 O’Donnell KA, "c-Myc-regulated microRNAs modulate E2F1 expression" 435 : 839-843, 2005

3 Hartman J, "Tumor repressive functions of estrogen receptor B in SW480 colon cancer cells" 69 : 6100-6106, 2009

4 Pan Q, "The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression" 13 : 797-806, 2007

5 Hall JM, "The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens" 140 : 5566-5578, 1999

6 Cummins JM, "The colorectal microRNAome" 103 : 3687-3692, 2006

7 Ries LA, "The annual report to the nation on the status of cancer" 88 : 2398-2424, 2000

8 Johnson SM, "RAS is regulated by the let-7 microRNA family" 120 : 635-647, 2005

9 Qiu Y, "Oestrogen induced apoptosis in colonocytes expressing oestrogen receptor β" 174 : 369-377, 2002

10 Valeri N, "Modulation of mismatch repair and genomic stability by miR-155" 107 : 6982-6987, 2010

11 Lee YS, "MicroRNAs in cancer" 4 : 199-227, 2009

12 Valeri N, "MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)" 107 : 21098-21103, 2010

13 Lu LF, "MicroRNA in the immune system, microRNA as an immune system" 127 : 291-298, 2009

14 Wu WK, "MicroRNA in colorectal cancer: from benchtop to bedside" 32 : 247-253, 2011

15 Koga Y, "MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening" 3 : 1435-1442, 2010

16 Wang Y, "MicroRNA and cancer-focus on apoptosis" 13 : 12-23, 2009

17 Yuki D, "Isolation of LEM domain-containing 1, a novel testisspecific gene expressed in colorectal cancers" 12 : 275-280, 2004

18 Bandres E, "Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues" 5 : 29-, 2006

19 Sarver AL, "Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states" 9 : 401-, 2009

20 Link A, "Fecal MicroRNAs as novel biomarkers for colon cancer screening" 19 : 1766-1774, 2010

21 Slattery ML, "Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer" 61 : 126-130, 2001

22 Maria M, "Estrogen receptor mediates the protective effects of estrogen in colon cancer" 6 : 149-162, 2008

23 Wilkins HR, "Estrogen prevents sustained COLO-205 human colon cancer cell growth by inducing apoptosis, decreasing c-myb protein, and decreasing transcription of the anti-apoptotic protein bcl-2" 31 : 16-22, 2010

24 Chlebowski RT, "Estrogen plus Progestin and colorectal cancer in postmenopausal women" 350 : 991-1004, 2004

25 Jin P, "Estrogen Stimulates the Expression of Mismatch Repair Gene hMLH1 in Colonic Epithelial Cells" 3 : 910-916, 2010

26 Wickramasinghe NS, "Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells" 37 : 2584-2595, 2009

27 Ferlay J, "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008" 127 : 2893-2917, 2010

28 Earle JS, "Association of microrna expression with microsatellite instability status in colorectal adenocarcinoma" 12 : 433-440, 2010

29 Jones AM, "Array-CGH analysis of microsatellite-stable, near-diploid bowel cancers and comparison with other types of colorectal carcinoma" 24 : 118-129, 2005

30 Douglas EJ, "Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas" 64 : 4817-4825, 2004

31 Pfaffl MW, "A new mathematical model for relative quantification in real-time RT-PCR" 29 : e45-, 2001

32 He L, "A microRNA polycistron as a potential human oncogene" 435 : 828-833, 2005

33 Volinia S, "A microRNA expression signature of human solid tumors defines cancer gene targets" 103 : 2257-2261, 2006

34 Froggatt NJ, "A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer" 36 : 97-102, 1999

35 Perillo B, "17β-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence" 20 : 2890-2901, 2000