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ABSTRACT Metastasis in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254
miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231),
metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty
miRNAs were upregulated and seven were downregulated in metastatic cancer cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently
downregulated in metastatic cancer cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into
cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 5′-untranslated region of an open
reading frame C17orf91, and the promoter/enhancer of C17orf91 drives miR-22 expression. We observed elevated C17orf91 expression in non-basal subtype compared with basal subtype breast
cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results
suggest that metastatic cancer cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasis-specific oncogenic pathways may help to
manipulate tumor behavior and aid in the design of more effective targeted therapies. Access through your institution Buy or subscribe This is a preview of subscription content, access via
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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MOLECULAR PATHOGENESIS OF BREAST CANCER: IMPACT OF _MIR-99A-5P_
AND _MIR-99A-3P_ REGULATION ON ONCOGENIC GENES Article 12 November 2020 TRIPLE NEGATIVE AGGRESSIVE PHENOTYPE CONTROLLED BY MIR-135B AND MIR-365: NEW THERANOSTICS CANDIDATES Article Open
access 22 March 2021 ROLES OF MIR-20A-5P IN BREAST CANCER BASED ON THE CLINICAL AND MULTI-OMIC (CAMO) COHORT AND IN VITRO STUDIES Article Open access 23 October 2024 ACCESSION CODES
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is supported by Indiana University Simon Cancer Center Pilot grant and by Komen for Cure grant BCTR0601111 to HN. JBP and RMB are supported by National Institutes of Health Training Grants
T32 DK07519 and T32 CA111198, respectively. HN is Marian J Morrison Professor of Breast Cancer Research. AUTHOR INFORMATION Author notes * J B Patel and H N Appaiah: These authors
contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA J B Patel, H N Appaiah, R M Burnett, P
Bhat-Nakshatri & H Nakshatri * Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA G Wang & Y Liu * Department of Pathology, Indiana University
School of Medicine, Indianapolis, IN, USA R Mehta & S Badve * Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical School, Nashville, TN, USA M J
Thomson * Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA S Hammond * Laboratory of Molecular
Pharmacology, Center for Cancer Research National Cancer Institute, Bethesda, MD, USA P Steeg * Department of Biochemistry and Molecular Biology, Indiana University School of Medicine,
Indianapolis, IN, USA H Nakshatri Authors * J B Patel View author publications You can also search for this author inPubMed Google Scholar * H N Appaiah View author publications You can also
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declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Patel, J., Appaiah, H., Burnett, R. _et al._ Control of EVI-1 oncogene
expression in metastatic breast cancer cells through microRNA miR-22. _Oncogene_ 30, 1290–1301 (2011). https://doi.org/10.1038/onc.2010.510 Download citation * Received: 06 May 2010 *
Revised: 30 September 2010 * Accepted: 30 September 2010 * Published: 08 November 2010 * Issue Date: 17 March 2011 * DOI: https://doi.org/10.1038/onc.2010.510 SHARE THIS ARTICLE Anyone you
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Springer Nature SharedIt content-sharing initiative KEYWORDS * breast cancer * metastasis * microRNA * miR-22 * let-7