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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor α in breast cancer cells
Cancer Research, Volume 70, No. 22, Year 2010
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Description
Estrogen receptor α (ERα) upregulation causes abnormal cell proliferation in about two thirds of breast cancers, yet understanding of the underlying mechanisms remains incomplete. Here, we show that high expression of the microRNA miR-375 in ERα-positive breast cell lines is a key driver of their proliferation. miR-375 overexpression was caused by loss of epigenetic marks including H3K9me2 and local DNA hypomethylation, dissociation of the transcriptional repressor CTCF from the miR-375 promoter, and interactions of ERα with regulatory regions of miR-375. Inhibiting miR-375 in ERα-positive MCF-7 cells resulted in reduced ERα activation and cell proliferation. A combination of expression profiling from tumor samples and miRNA target prediction identified RASD1 as a potential miR-375 target. Mechanistic investigations revealed that miR-375 regulates RASD1 by targeting the 3′ untranslated region in RASD1 mRNA. Additionally, we found that RASD1 negatively regulates ERα expression. Our findings define a forward feedback pathway in control of ERα expression, highlighting new strategies to treat ERα-positive invasive breast tumors. ©2010 AACR.
Authors & Co-Authors
Rocha Simonini, Pedro De Souza
Germany, Heidelberg
German Cancer Research Center
Germany, Heidelberg
Universität Heidelberg
Breiling, Achim
Germany, Heidelberg
Dkfz-zmbh-allianz
Gupta, Nibedita
Germany, Heidelberg
German Cancer Research Center
Malekpour, Mahdi
Iran, Tehran
Imam Khomeini Hospital
Youns, Mahmoud Moustafa
Germany, Heidelberg
German Cancer Research Center
Egypt, Helwan
Faculty of Pharmacy
Omranipour, Ramesh
Iran, Tehran
Imam Khomeini Hospital
Ghorbani, Fariba
Iran, Tehran
Shohadaye Tajrish Educational Hospital
Volinia, Stefano
Italy, Ferrara
University of Ferrara
Croce, Carlo Maria
United States, Columbus
The Ohio State University Comprehensive Cancer Center
Najmabadi, Hossein
Iran, Tehran
University of Social Welfare and Rehabilitation Sciences
Diederichs, Sven
Germany, Heidelberg
Universität Heidelberg
Sahin, Özgür
Germany, Heidelberg
German Cancer Research Center
Mayer, Doris
Germany, Heidelberg
German Cancer Research Center
Lyko, Frank
Germany, Heidelberg
Dkfz-zmbh-allianz
Hoheisel, Jörg D.
Germany, Heidelberg
German Cancer Research Center
Riazalhosseini, Yasser
Germany, Heidelberg
German Cancer Research Center
Statistics
Citations: 262
Authors: 16
Affiliations: 9
Identifiers
Doi:
10.1158/0008-5472.CAN-10-1318
ISSN:
00085472
e-ISSN:
15387445
Research Areas
Cancer
Genetics And Genomics