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Br J Cancer. 2014 Apr 15;110(8):2072-80. doi: 10.1038/bjc.2014.113. Epub 2014 Feb 27.

Identifying microRNAs regulating B7-H3 in breast cancer: the clinical impact of microRNA-29c.

Author information

1
Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, N-0310 Oslo, Norway.
2
1] Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, N-0310 Oslo, Norway [2] Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, N-0424 Oslo, Norway.
3
Medical Biotechnology, VTT Technical Research Centre of Finland, FI-20520 Turku, Finland.
4
1] Department of Genetics, Institute of Cancer Research, Oslo University Hospital, N-0310 Oslo, Norway [2] The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway.
5
Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
6
1] Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, N-0424 Oslo, Norway [2] Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
7
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, N-0424 Oslo, Norway.
8
1] Department of Genetics, Institute of Cancer Research, Oslo University Hospital, N-0310 Oslo, Norway [2] The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway [3] Department of Research, Vestre Viken Hospital Trust, N-3004 Drammen, Norway.

Abstract

BACKGROUND:

B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 and assess their potential prognostic implications in breast cancer.

METHODS:

MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3'-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients).

RESULTS:

We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3'-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts.

CONCLUSIONS:

We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.

PMID:
24577056
PMCID:
PMC3992492
DOI:
10.1038/bjc.2014.113
[Indexed for MEDLINE]
Free PMC Article

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