title: Overexpression of TNKS1BP1 in lung cancers and its involvement in homologous recombination pathway of DNA double-strand breaks.
abstract: TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double-strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy.
authors.affiliation: XiangYa School of Public Heath, Central South University, Changsha, Hunan Province, 410078, China.|National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing, 102206, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Beijing Key Laboratory for Radiobiology, Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guan
authors.affiliation: Beijing Key Laboratory for Radiobiology, Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Lian-Hong
authors.initials: LH
authors.lastname: Zou
authors.affiliation: Beijing Key Laboratory for Radiobiology, Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory for Radiobiology, Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Institute for Environmental Medicine and Radiation Hygiene, The College of Public Health, University of South China, Hengyang, Hunan Province, 421000, China.
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Rang
authors.affiliation: Beijing Key Laboratory for Radiobiology, Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.|Institute for Environmental Medicine and Radiation Hygiene, The College of Public Health, University of South China, Hengyang, Hunan Province, 421000, China.
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 100039, China.|National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing, 102206, China.
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Pei
authors.affiliation: XiangYa School of Public Heath, Central South University, Changsha, Hunan Province, 410078, China.
authors.forename: Cai-Gao
authors.initials: CG
authors.lastname: Zhong
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D001761:Bleomycin / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D053903:DNA Breaks, Double-Stranded; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D059767:Recombinational DNA Repair; D016019:Survival Analysis; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C455625:TNKS1BP1 protein, human; D035321:Telomeric Repeat Binding Protein 1; D001761:Bleomycin; D002945:Cisplatin
keywords: DNA homologous recombination; Lung adenocarcinoma (LAC); TNKS1BP1; cell cycle; chemotherapy