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Genome Med. 2015 Feb 2;7(1):21. doi: 10.1186/s13073-015-0135-5. eCollection 2015.

Integrated analysis reveals microRNA networks coordinately expressed with key proteins in breast cancer.

Author information

1
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310 Norway ; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, 0316 Norway.
2
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310 Norway ; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, 0316 Norway ; Department of Oncology, Division of Surgery, Cancer and Transplantation, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310 Norway.
3
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310 Norway ; Centre for Cancer Biomedicine, University of Oslo, Oslo, 0316 Norway ; Department of Computer Science, University of Oslo, Oslo, 0316 Norway.
4
Institute of Clinical Medicine, University of Oslo, Oslo, 0316 Norway.
5
Department of Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA.
6
K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, 0316 Norway ; Department of Research, Vestre Viken Hospital Trust, Drammen, 3004 Norway.
7
K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, 0316 Norway ; Centre for Cancer Biomedicine, University of Oslo, Oslo, 0316 Norway ; Department of Computer Science, University of Oslo, Oslo, 0316 Norway.
8
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310 Norway ; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, 0316 Norway ; Department of Clinical Molecular Biology and Laboratory Science (EpiGen), Division of Medicine, Akershus University Hospital, Lørenskog, 1478 Norway.

Abstract

BACKGROUND:

The role played by microRNAs in the deregulation of protein expression in breast cancer is only partly understood. To gain insight, the combined effect of microRNA and mRNA expression on protein expression was investigated in three independent data sets.

METHODS:

Protein expression was modeled as a multilinear function of powers of mRNA and microRNA expression. The model was first applied to mRNA and protein expression for 105 selected cancer-associated genes and to genome-wide microRNA expression from 283 breast tumors. The model considered both the effect of one microRNA at a time and all microRNAs combined. In the latter case the Lasso penalized regression method was applied to detect the simultaneous effect of multiple microRNAs.

RESULTS:

An interactome map for breast cancer representing all direct and indirect associations between the expression of microRNAs and proteins was derived. A pattern of extensive coordination between microRNA and protein expression in breast cancer emerges, with multiple clusters of microRNAs being associated with multiple clusters of proteins. Results were subsequently validated in two independent breast cancer data sets. A number of the microRNA-protein associations were functionally validated in a breast cancer cell line.

CONCLUSIONS:

A comprehensive map is derived for the co-expression in breast cancer of microRNAs and 105 proteins with known roles in cancer, after filtering out the in-cis effect of mRNA expression. The analysis suggests that group action by several microRNAs to deregulate the expression of proteins is a common modus operandi in breast cancer.

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