VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

Shaymaa E. El Feky^1, , Fawziya A.R. Ibrahim², Adel Nassar³, Nadia A. Abd El Moneim⁴, Samia A. Ebeid², Mohammad A. Ahmad⁵, Sanaa Shawky⁶ and Mohammad M. Nasef³

¹Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

²Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

³Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt

⁴Cancer Management and Research Department, Medical Research Institute, University of Alexandria, Egypt

⁵Military Medical Academy, Alexandria, Egypt

⁶Pathology Department, Medical Research Institute, University of Alexandria, Egypt

Cite this paper:
Shaymaa E. El Feky, Fawziya A.R. Ibrahim, Adel Nassar, Nadia A. Abd El Moneim, Samia A. Ebeid, Mohammad A. Ahmad, Sanaa Shawky and Mohammad M. Nasef. VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer. Journal of Cancer Research and Treatment. 2019; 7(1):10-16. doi: 10.12691/jcrt-7-1-2

Abstract

Triple negative is a subtype of breast cancer characterized by lack of expression of hormone receptors (ER, PR and Her2/neu). Due to the limited treatment options, the search for novel treatment targets continues. The aim of this study was to assess the differential expression of miR-206, VEGF and KRAS in TNBC and non-TNBC tissues and cell lines and to evaluate the modulatory effect of miR-206 on the key oncogenic targets VEGF and KRAS. The expression of miR-206, VEGF and KRAS was quantified using real time PCR in both paraffin embedded breast cancer and adjacent tissues as well as in MDA-MB-231 and MCF-7 cell lines. Cell lines were transfected with different concentrations of miR-206 mimic and their viability were assessed using MTT assay. Our results indicated that miR-206 was significantly downregulated in cancerous compared to non-cancerous tissues with a more pronounced downregulation in TNBC than non-TNBC tissues. VEGF and KRAS were significantly upregulated in TNBC compared to non-TNBC and their expression was negatively correlated to miR-206 expression. Transfection of TNBC and non-TNBC cell lines with miR-206 mimic resulted in a dose dependent reduction in cell viability as well as a significant reduction in VEGF and KRAS expression. In conclusion, based on our combined human tissues and cell line-based investigations we can suggest that VEGF and KRAS may be potential targets for miR-206-mediated regulation and that their targeting by miR-206 can be a highly efficient therapeutic strategy in TNBC.

Keywords:
triple negative breast cancer miR-206 VEGF KRAS epigenetic regulation

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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