title: DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses.
abstract: Radiotherapy resistance is one of the major factors limiting the efficacy of radiotherapy in lung cancer patients. The extensive investigations indicate the diversity in the mechanisms underlying radioresistance. Here, we revealed that DNA damage binding protein 2 (DDB2) is a potential regulator in the radiosensitivity of non-small cell lung cancer (NSCLC) cells. DDB2, originally identified as a DNA damage recognition factor in the nucleotide excision repair, promotes the survival and inhibits the apoptosis of NSCLC cell lines upon ionizing radiation (IR). Mechanistic investigations demonstrated that DDB2 is able to facilitate IR-induced phosphorylation of Chk1, which plays a critical role in the cell cycle arrest and DNA repair in response to IR-induced DNA double-strand breaks (DSBs). Indeed, knockdown of DDB2 compromised the G2 arrest in the p53-proficient A549 cell line and reduced the efficiency of homologous recombination (HR) repair. Taken together, our data indicate that the expression of DDB2 in NSCLC could be used as a biomarker to predict radiosensitivity of the patients. Targeting Chk1 can be used to increase the efficacy of radiotherapy in patients of NSCLC possessing high levels of DDB2.
authors.affiliation: Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China.|Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zou
authors.affiliation: Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.|Dublin Coffman High School, Dublin, OH, 43017, USA.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cui
authors.affiliation: Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Department of Pharmacology, Weifang Medical University, Weifang, Shandong, 261053, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Qu
authors.affiliation: Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Oncology, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China.
authors.forename: Shaozhong
authors.initials: S
authors.lastname: Wei
authors.affiliation: Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China. zyfcn@yahoo.com.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA. qi-en.wang@osumc.edu.
authors.forename: Qi-En
authors.identifier: http://orcid.org/0000-0002-3759-2148
authors.initials: QE
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D059767:Recombinational DNA Repair / Q000235:genetics* / Q000528:radiation effects; D014407:Tumor Cells, Cultured
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins
keywords: Chk1; DDB2; Homologous recombination; NSCLC; Radioresistance