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Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels

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Abstract

Background

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Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3).

Objectives

The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors.

Methods

In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) using TaqMan® technology and immunohistochemistry.

Results

miR-221/222 levels varied significantly across groups based on invasiveness (P < 0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = −0.714, and P = 0.013, r = −0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = −0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively).

Conclusion

An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.

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Author information

Authors and Affiliations

  1. Department for Radiobiology and Molecular Genetics, University of Belgrade-Vinca Institute of Nuclear Sciences, Mike Petrovica Alasa 12-14, 11001, Belgrade, Serbia

    Nina Petrovic, Radoslav Davidovic, Snezana Jovanovic-Cupic & Milena Krajnovic

  2. Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia

    Silvana Lukic

  3. Clinic of Maxillofacial Surgery, School of Dental Medicine, University of Belgrade, Dr. Subotica 4, 11000, Belgrade, Serbia

    Milan Petrovic

  4. Department of Pharmacology, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000, Belgrade, Serbia

    Jelena Roganovic

Authors
  1. Nina Petrovic
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  2. Radoslav Davidovic
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  3. Snezana Jovanovic-Cupic
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  4. Milena Krajnovic
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  5. Silvana Lukic
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  6. Milan Petrovic
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  7. Jelena Roganovic
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Corresponding author

Correspondence to Nina Petrovic.

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Conflicts of interest

All of the authors (NP, RD, SJ-C, MK, SL, MP, JR) declare that they have no conflicts of interest.

Funding

This work was supported by the Ministry of Education and Science, Republic of Serbia (Grant Numbers ON173049 and 175021).

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Petrovic, N., Davidovic, R., Jovanovic-Cupic, S. et al. Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels. Mol Diagn Ther 20, 603–615 (2016). https://doi.org/10.1007/s40291-016-0230-3

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  • DOI: https://doi.org/10.1007/s40291-016-0230-3

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