Estrogen receptor β expression induces changes in the microRNA pool in human colon cancer cells
2013 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, no 7, 1431-41 p.Article in journal (Refereed) Published
There is epidemiological, animal and in vitro evidence that estrogen receptor β (ERβ) can mediate protective effects against colon cancer, but the mechanism is not completely understood. Previous research has indicated critical pathways whereby ERβ acts in an antitumorigenic fashion. In this study, we investigate ERβ's impact on the microRNA (miRNA) pool in colon cancer cells using large-scale genomic approaches, bioinformatics and focused functional studies. We detect and confirm 27 miRNAs to be significantly changed following ERβ expression in SW480 colon cancer cells. Among these, the oncogenic miR-17-92 cluster and miR-200a/b are strongly downregulated. Using target prediction and anticorrelation to gene expression data followed by focused mechanistic studies, we demonstrate that repression of miR-17 is a secondary event following ERβ's downregulatory effect on MYC. We show that re-introduction of miR-17 can reverse the antiproliferative effects of ERβ. The repression of miR-17 also influences cell death upon DNA damage and mediates regulation of NCOA3 (SRC-3) and CLU in colon cancer cells. We further determine that the downregulation of miR-200a/b mediates increased ZEB1 while decreasing E-cadherin levels in ERβ-expressing colon cancer cells. Changes in these genes correspond to significant alterations in morphology and migration. Our work contributes novel data of ERβ and miRNA in the colon. Elucidating the mechanism of ERβ and biomarkers of its activity has significant potential to impact colon cancer prevention and treatment.
Place, publisher, year, edition, pages
2013. Vol. 34, no 7, 1431-41 p.
Cell and Molecular Biology
Research subject SRA - Molecular Bioscience
IdentifiersURN: urn:nbn:se:kth:diva-165353DOI: 10.1093/carcin/bgt067ISI: 000321753000003PubMedID: 23436804ScopusID: 2-s2.0-84880285292OAI: oai:DiVA.org:kth-165353DiVA: diva2:808112
FunderSwedish Cancer SocietyKnut and Alice Wallenberg Foundation
QC 201505072015-04-272015-04-272015-05-07Bibliographically approved