Expression of DNA damage checkpoint 53BP1 is correlated with prognosis cell proliferation and apoptosis in colorectal cancer

摘要

53BP1, an important mediator of DNA damage checkpoint, plays an essential role in maintaining the cell genome stability, and the aberrant expression of 53BP1 was found to contribute to tumor occurrence and development. In this study, we explored the clinical significance of 53BP1 expression in colorectal cancer and investigated the effects of 53BP1 expression on tumor cell proliferation and apoptosis and its possible mechanisms. Immunohistochemical analysis was performed to detect the expression of 53BP1 in 95 cases of tumor tissues. After establishment of shRNA-mediated knockdown stable HCT-116 cell lines, cell proliferation, apoptosis and cell cycle distribution were detected by MTT and flow cytometry, and expression of up-and down-steam related proteins as γ-H2AX, CHK2 and P53 were tested by Western blot. 53BP1 intensity was found to be associated with tumor location (P < 0.05), and the low expression of 53BP1 revealed decreased survival time compared with high expression in subgroups as male, tumor size > 5 cm, tumor located at right side, T stage as T3-T4, N0, clinical stage as I-II (P < 0.05). In vitro, shRNA-mediated loss of 53BP1 obviously inhibited HCT-116 tumor cell apoptosis, promoted cell proliferation and increased accumulation of cells in S phase. Meanwhile, the expression of γ-H2AX, CHK2 and P53 was significantly reduced (P < 0.05). Our findings suggest 53BP1 may serve as a candidate biomarker for predicting prognosis and disease development in colorectal cancer.