Hu Tingting, Weng Shuqiang, Tang Wenqing, Xue Ruyi, Chen She, Cai Guoxiang, Cai Yu, Shen Xizhong, Zhang Si, Dong Ling
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
PLoS One. 2015 May 1;10(5):e0125281. doi: 10.1371/journal.pone.0125281. eCollection 2015.
Inhibitors of apoptosis proteins (IAPs) have been well investigated in human cancers, where they are frequently overexpressed and associated with poor prognosis. Here we explored the role of baculoviral IAP repeat containing 6 (BIRC6), a member of IAPs, in human colorectal cancer (CRC).
We used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.
We reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.
Taken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.
凋亡抑制蛋白(IAPs)在人类癌症中已得到充分研究,在这些癌症中它们经常过度表达并与不良预后相关。在此,我们探讨了IAPs成员之一含杆状病毒IAP重复序列6(BIRC6)在人类结直肠癌(CRC)中的作用。
我们使用蛋白质免疫印迹法和免疫组织化学法检测7种CRC细胞系和126例CRC临床样本中BIRC6的表达。我们通过慢病毒介导的沉默方法确定BIRC6在CRC细胞系中的生物学意义。
我们报道BIRC6在CRC细胞系和临床CRC组织中过度表达。BIRC6的过度表达与CRC的肿瘤大小和浸润深度相关。BIRC6的过度表达与较差的总生存期(OS)(P = 0.001)和较短的无病生存期(DFS)(P = 0.010)相关。BIRC6敲低抑制细胞增殖,使细胞周期停滞在S期,下调细胞周期蛋白A2、B1、D1和E1水平,并使CRC细胞在体外和体内对化疗敏感。
综上所述,这些数据表明BIRC6的过度表达是结直肠癌预后不良的一个预测指标,并且BIRC6可能是CRC治疗的一个潜在靶点。