Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

J. B. Patel, H. N. Appaiah, R. M. Burnett, P. Bhat-Nakshatri, G. Wang, R. Mehta, Sunil Badve, M. J. Thomson, S. Hammond, P. Steeg, Yunlong Liu, Harikrishna Nakshatri

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1290-1301
Number of pages12
JournalOncogene
Volume30
Issue number11
DOIs
StatePublished - Mar 17 2011

Fingerprint

MicroRNAs
Oncogenes
Breast Neoplasms
Neoplasms
Down-Regulation
Neoplasm Metastasis
Cell Line
Validation Studies
5' Untranslated Regions
Microarray Analysis
Adrenal Glands
Nude Mice
Estrogen Receptors
Open Reading Frames
Lung Diseases
Adipose Tissue
Breast
Bone and Bones
Brain
Proteins

Keywords

  • breast cancer
  • let-7
  • metastasis
  • microRNA
  • miR-22

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Patel, J. B., Appaiah, H. N., Burnett, R. M., Bhat-Nakshatri, P., Wang, G., Mehta, R., ... Nakshatri, H. (2011). Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene, 30(11), 1290-1301. https://doi.org/10.1038/onc.2010.510

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. / Patel, J. B.; Appaiah, H. N.; Burnett, R. M.; Bhat-Nakshatri, P.; Wang, G.; Mehta, R.; Badve, Sunil; Thomson, M. J.; Hammond, S.; Steeg, P.; Liu, Yunlong; Nakshatri, Harikrishna.

In: Oncogene, Vol. 30, No. 11, 17.03.2011, p. 1290-1301.

Research output: Contribution to journalArticle

Patel, JB, Appaiah, HN, Burnett, RM, Bhat-Nakshatri, P, Wang, G, Mehta, R, Badve, S, Thomson, MJ, Hammond, S, Steeg, P, Liu, Y & Nakshatri, H 2011, 'Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22', Oncogene, vol. 30, no. 11, pp. 1290-1301. https://doi.org/10.1038/onc.2010.510
Patel JB, Appaiah HN, Burnett RM, Bhat-Nakshatri P, Wang G, Mehta R et al. Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene. 2011 Mar 17;30(11):1290-1301. https://doi.org/10.1038/onc.2010.510
Patel, J. B. ; Appaiah, H. N. ; Burnett, R. M. ; Bhat-Nakshatri, P. ; Wang, G. ; Mehta, R. ; Badve, Sunil ; Thomson, M. J. ; Hammond, S. ; Steeg, P. ; Liu, Yunlong ; Nakshatri, Harikrishna. / Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. In: Oncogene. 2011 ; Vol. 30, No. 11. pp. 1290-1301.
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