title: Downregulation of MDC1 and 53BP1 by short hairpin RNA enhances radiosensitivity in laryngeal carcinoma cells.
abstract: DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are among the most cytotoxic types of DNA damage. The DNA damage response (DDR) may be a reason for the cancer cell resistance to radiotherapy using IR. Identified as critical upstream mediators of the phosphorylation of ataxia telangiectasia-mutated (ATM) pathway, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding proteins 1 (53BP1) may affect the radiosensitivity of tumor cells. In the present study, we generated two HEP-2 cell lines with a stable knockdown of MDC1 or 53BP1 with short hairpin RNA (shRNA), respectively, and investigated the effect of MDC1 and 53BP1 on cell radiosensitivity, cell cycle distribution and the formation of cell foci. Downregulation of the two proteins reduced the number of clonogenic cells that treated with IR. Accumulation of G2/M phase cells was detected after the MDC1 and 53BP1 downregulation. These results indicated that the expression of MDC1 or 53BP1 limited tumor cell sensitivity to radiotherapy and may play an important role in the DNA repair progression. Furthermore, the MDC1 foci was identified and presented in the 53BP1-inhibited cells. By contrast, the 53BP1 foci was absent from the MDC1-inhibited cells. The results confirmed that the recruitment of 53BP1 into the foci occurred in an MDC1-dependent manner.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qiheng
authors.initials: Q
authors.lastname: Gou
authors.affiliation: Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China.
authors.forename: Keqi
authors.initials: K
authors.lastname: Xie
authors.affiliation: Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C498301:TP53BP1 protein, human; D015534:Trans-Activators; D000071857:Tumor Suppressor p53-Binding Protein 1