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Erschienen in:
30.01.2017 | Original Article
miR-668 enhances the radioresistance of human breast cancer cell by targeting IκBα
Erschienen in: Breast Cancer | Ausgabe 5/2017
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Background
A large proportion of breast cancer patients are resistant to radiotherapy, which is a mainstay treatment for this malignancy, but the mechanisms of radioresistance remain unclear.
Methods and materials
To evaluate the role of miRNAs in radioresistance, we established two radioresistant breast cancer cell lines MCF-7R and T-47DR derived from parental MCF-7 and T-47D. Moreover, miRNA microarray, quantitative RT-PCR analysis, luciferase reporter assay and western blotting were used.
Results
We found that miR-668 was most abundantly expressed in radioresistant cells MCF-7R and T-47DR. miR-668 knockdown reversed radioresistance of MCF-7R and T-47DR, miR-668 overexpression enhanced radioresistance of MCF-7 and T-47D cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated IκBα, a tumor-suppressor as well as an NF-κB inhibitor, was a direct target of miR-668. Further, miR-668 overexpression inhibited IκBα expression, activated NF-κB, thus, increased radioresistance of MCF-7 and T-47D cells. Conversely, miR-668 knockdown restored IκBα expression, suppressed NF-κB, increased radiosensitivity of MCF-7R and T-47DR cells.
Conclusion
Our findings suggest miR-668 is involved in the radioresistance of breast cancer cells and miR-668-IκBα-NF-κB axis may be a novel candidate for developing rational therapeutic strategies for human breast cancer treatment.