Πέμπτη 5 Ιανουαρίου 2017

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.

Thumbnail image of graphical abstract

TNKS1BP1 is overexpressed in human lung adenocarcinoma (LAC) and correlated with the LAC patients’ survival. TNKS1BP1 presents a potential new biomarker for LAC. TNKS1BP1 regulates the genomic stability and cellular sensitivity to DNA damage agents in A549s, and is associated with its function in regulating HR repair of DNA double-strand breaks.



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