miR-668 enhances the radioresistance of human breast cancer cell by targeting IκBα

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. 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. 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 I kappa B alpha, a tumor-suppressor as well as an NF-kappa B inhibitor, was a direct target of miR-668. Further, miR-668 overexpression inhibited I kappa B alpha expression, activated NF-kappa B, thus, increased radioresistance of MCF-7 and T-47D cells. Conversely, miR-668 knockdown restored I kappa B alpha expression, suppressed NF-kappa B, increased radiosensitivity of MCF-7R and T-47DR cells. Our findings suggest miR-668 is involved in the radioresistance of breast cancer cells and miR-668-I kappa B alpha-NF-kappa B axis may be a novel candidate for developing rational therapeutic strategies for human breast cancer treatment.