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Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations

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Abstract

The genetic factors of cancer predisposition remain elusive in the majority of familial and/or early-onset cases of breast cancer (BC). This type of BC is promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other hand, recent studies have indicated that alterations in the levels of miRNA expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations have been reported to commonly lead to alterations in genes that encode cancer-related proteins, little is known regarding the putative impact of these mutations on noncoding miRNAs. In the present study, we aimed to determine whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC. An expression analysis of 14 human miRNAs previously shown to be related to BC diagnosis, prognosis, and drug resistance was conducted using tissues from 60 familial and/or early-onset patients whose peripheral blood samples had been screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation compared with those of patients without a BRCA mutation (P = 0.04 and P = 0.02, respectively). Our results defined the associations between the expression status of let-7a and miR-335 and BRCA mutations. The expression analysis of these miRNAs might be used as biomarkers of the BRCA mutation status of early-onset and/or familial BC.

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Abbreviations

BC:

Breast cancer

ER:

Estrogen receptor

PR:

Progesterone receptor

HER-2:

Human epidermal growth factor receptor 2

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Acknowledgments

We would like to thank Professor Kay Huebner for her scientific advice and careful reading of the draft manuscript. Additionally, we thank Professor Huebner and Professor Hansjuerg Alder in the Molecular Virology, Immunology and Medical Genetics Human Cancer Genetics Program, Department of the Ohio State University, who kindly performed the RT-PCR experimental stage in the Comprehensive Cancer Center for in this study. This study was supported by a grant from the Scientific Research Projects Foundation (BAP) of the Uludag University of Turkey [Project No: UAP(T)-2011/1].

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medical Biology, Institute of Health Sciences, Uludag University, Bursa, Turkey

    Elif Erturk & Gulcin Tezcan

  2. Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey

    Gulsah Cecener, Unal Egeli & Berrin Tunca

  3. Department of General Surgery, Faculty of Medicine, University of Uludag, Bursa, Turkey

    Sehsuvar Gokgoz & Ismet Tasdelen

  4. Department of Pathology, Faculty of Medicine, University of Uludag, Bursa, Turkey

    Sahsine Tolunay

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  1. Elif Erturk
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  2. Gulsah Cecener
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  3. Unal Egeli
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  4. Berrin Tunca
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  5. Gulcin Tezcan
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  6. Sehsuvar Gokgoz
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Correspondence to Gulsah Cecener.

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E. Erturk and G. Cecener have contributed equally to this work.

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Erturk, E., Cecener, G., Egeli, U. et al. Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations. Mol Cell Biochem 395, 77–88 (2014). https://doi.org/10.1007/s11010-014-2113-4

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  • DOI: https://doi.org/10.1007/s11010-014-2113-4

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