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The role of microRNA in resistance to breast cancer therapy

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MicroRNAs (miRNAs) are small noncoding RNA molecules with big implications in cancer. The abnormal expression of specific miRNAs has been linked to development of many cancer types. Dysregulated miRNAs play a significant role in proliferation, invasion, differentiation, apoptosis, and resistance of various cancer cells, and considered as oncogenes or tumor‐suppressor genes. Findings have shown abnormal expression of specific miRNAs in breast tumors is a strong indication about the resistance to conventional cancer therapy methods. Acquired cancer resistance is a complex, multifactorial occurrence that requires various mechanisms and processes, however, recent studies have suggested that resistance may be linked to treatment‐induced dysregulation of miRNAs. This dysregulation of miRNAs can affect the protein expression in cells, the ability for anti‐cancer drugs to reach their targets within cells, and the apoptotic pathways. Controlling the expression of these miRNAs alters the resistant phenotype of breast cancer to a nonresistant one. This review focuses on the role of dysregulated miRNAs in breast cancer that are linked to resistance against chemo‐, radiation, hormone, and targeted therapies. Finally, the role of miRNAs in breast cancer metastasis is briefly discussed. WIREs RNA 2014, 5:823–833. doi: 10.1002/wrna.1248

Effects of miR‐302 overexpression in radiosensitivity in vivo. Xenografts in mice derived from miR‐302a‐transfected MDA‐MB‐231RR and control vector infected were irradiated, with a strong dosage of 5 Gy or a mock dosage of 1 Gy, to view the efficacy of miR‐302a in resensitizing tumors. The cells that were transfected with miR‐302a and given high radiation doses showed a drastic decrease in tumor volume, while the controls and mock radiation levels did not. (Reprinted with permission from Ref . Copyright 2013 Springer)
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Prevention of breast cancer metastasis by targeting miR‐10b. (a) A schematic of the nanodrug targeting miRNA‐10b (MN‐anti‐miR10b). The nanodrug consists of magnetic nanoparticles conjugated to Cy5.5 dye, a tumor‐targeting peptide (cRGD) and a knock‐down LNA oligonucleotide targeting human miRNA‐10b. (b) qRT‐PCR shows that the nanodrug mediated a significant 87.8 ± 6.2% knock‐down of the target miR‐10b. (c) Representative bioluminescence images of tumor‐bearing mice treated with the anti‐miR10b for four weeks beginning prior to lymph node metastasis. The mice were treated either with the active MN‐anti‐miR10b or with inactive control MN‐scr‐miR. While the bioluminescence signal was visible in the brachial lymph nodes of control animals, the signals in the experimental animals was at pre‐metastatic levels, indicating prevention of metastasis by MN‐anti‐miR10b. (d) Quantitative analysis of bioluminescence images. Radiance (photons/sec) in the brachial lymph nodes of control mice treated with MN‐scr‐miR was significantly higher than in experimental animals treated with MN‐anti‐miR10b. (Reprinted with permission from Ref . Copyright 2013 Nature Publishing Group)
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