Tan Wei, Guan Hua, Zou Lian-Hong, Wang Yu, Liu Xiao-Dan, Rang Wei-Qing, Zhou Ping-Kun, Pei Hua-Dong, Zhong Cai-Gao
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.
Cancer Med. 2017 Feb;6(2):483-493. doi: 10.1002/cam4.995. Epub 2017 Jan 6.
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.
TNKS1BP1是聚（ADP - 核糖）聚合酶（PARP）超家族的成员。我们之前的研究表明，TNKS1BP1在DNA损伤反应中起重要作用。但TNKS1BP1是否以及如何与癌症相关仍不清楚。在此，我们发现TNKS1BP1在人肺腺癌（LAC）组织中上调，并且与LAC患者的总生存期（OS）较差相关。TNKS1BP1的失调影响了A549细胞对包括顺铂、博来霉素和电离辐射在内的几种DNA损伤剂的敏感性。机制上，TNKS1BP1的过表达增加了S期细胞的积累，同时伴随着M期细胞的减少。更重要的是，我们发现TNKS1BP1主要通过抑制RAD51焦点形成来影响DNA双链断裂的同源重组途径，从而调节基因组稳定性。总体而言，我们的研究表明在LAC中，TNKS1BP1的异常表达是常见事件，并且TNKS1BP1的过表达可能会影响癌症患者对化疗和放疗的结果。
