title: miR-668 enhances the radioresistance of human breast cancer cell by targeting IκBα.
abstract: 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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.|Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.|Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ding
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.|Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, China.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China. yaoherui@163.com.|Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, China. yaoherui@163.com.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China. yaoherui@163.com.
authors.forename: Herui
authors.initials: H
authors.lastname: Yao
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha
keywords: Breast cancer; IκBα; NF-κB; Radioresistance; miR-668